Plasma corticosterone 1 hr post 4/g/kg EtOH [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD. 	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci 	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	01	65-115 days	65	115	Male	5-15	µg/dl	16.21	1.63	20.29	3.02	17.42	1.67	16.89	2.14	22.63	3.22	12.53	2.86	13.97	1.86	28.12	2.81			24.68	2.55	17.17	1.91	23.09	1.42	16.11	2.53	27.64	2.69	20.39	4.06					16.41	2.49	20.13	1.91			22.82	3.16	15.07	4.75	24.24	3.18	24.03	2.00	16.34	2.04																													12/26/2002			ETCORT4(1H)		ETCORT1	EtOH	4g/kg		JKB/AR	p. 1202, Fig 1	MRG 020402 with JKB by publication	8748968.01
Plasma corticosterone 1 hr post saline [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci 	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	03	65-115 days	65	115	Male	3-9	µg/dl	4.36	0.64	4.07	1.71	4.35	2.00	8.28	3.78	3.99	1.03	8.59	4.62	15.19	5.56	5.07	0.89			5.64	1.90	2.47	0.64	6.14	1.14	6.04	2.67	7.54	3.74	1.09	0.37					5.66	2.71	4.22	0.69			6.95	1.58	11.34	8.21	11.86	9.09	7.77	2.66	2.88	0.53																													12/26/2002			SALCORT (1H)		SALCORT1	Saline			JKB/AR	p. 1202, Fig 1	MRG 020402 with JKB by publication	8748968.03
Plasma corticosterone 6 hr post ETOH Male [µg/dl] [Plasma corticosterone 6 hours post 4/g/kg EtOH (Male), Unpublished means from same series of studies as reported in:  Roberts, Phillips, Belknap, Finn, Keith 1995, Behavioral Neurosci 109:1199-1208]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci 	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	99	65-115 days	65	115	Male		µg/dl							16.4		15.3		13.9		4.5				4.7		21.9		17.7		16.5		17.7		15.3		20						13.3		12.8		16.1		14.8		8.6		21.5		16.3		11.8		18.1		9.5		15.7																								12/27/2002			SALCORT(6H)		ETCORT6	EtOH	4g/kg		JKB/AR		MRG 020402 with JKB	8748968.99
Plasma corticosterone 6 hr post EtOH Female [µg/dl] [Plasma corticosterone 6 hours post 4/g/kg EtOH (Female)Unpublished means from same series of studies as reported in:  Roberts, Phillips, Belknap, Finn, Keith 1995, Behavioral Neurosci 109:1199-1208]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	98	65-115 days	65	115	Female		µg/dl	5		9		4		9		14		8		4		10		5		22		18		12		17		7		20		13				13		9		16		12		8		21		16		12		18		10		16																								12/27/2002			SALCORT(6HF)		ETCORT6F	EtOH	4g/kg		JKB/AR		MRG 020402 with JKB	8748968.98
Audiogenic seizure-mean severity score in response to pure tone [severity of seizure] 		The difference in susceptibility to audiogenic seizures (AGS) between C57BL/6J and DBA/2J inbred strains of mice is due to multiple genetic factors. AGS susceptibility was tested in 21-day-old mice from classical crosses, BXD recombinant inbred (RI) strains, a congenic DBA/2N.B6N-Ahb inbred strain and crosses between the BXD RI strains and DBA/2J. Analysis of these data reveals that the variation in AGS susceptibility between these two strains results from allelic differences at three or more loci. Most of the variation is due to allelic differences at two loci. The first, Asp-1 (formerly Ias), is a major gene located on chromosome 12, between Ah and D12 Nyul. The second, Asp-2 (formerly asp), is a minor gene located on chromosome 4, tightly linked to b. The negative correlation of brain stem Ca2(+)-ATPase activity and AGS susceptibility in the BXD RI strains suggests that the strain difference in Ca2(+)-ATPase activity is inherited as a polygenic trait and that Asp-1 and Asp-2 are linked to, or identical to, factors that influence Ca2(+)-ATPase activity.	Neumann PE, Seyfried TN.	Mapping of two genes that influence susceptibility to audiogenic seizures in crosses of C57BL/6J and DBA/2J mice	Behav Genet 	20(2)	307-323	Mar	1990		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2141254&dopt=Abstract	2141254		01	20-22 days	20	22	MF	10-63	Severity of seizure; 0=no response, 1=wild running, 2=clonic or tonic seizure 	0.07		1.88		0.2		1.92		1.64		0.14		0.57		1.85		1.04		0.3		0.1		0.33		1.94		0.21		0.07		0.73				1.92				1.16		1.09		0.36		1.29		1		0.09		0				1.89																								6/23/2003	MK Sullivan	MK Sullivan	AGS		AGS	 	60 sec exposure to pure tone 11KHx at 120db		JKB	p. 311, Table 1	MRG 120601 from publication	2141254.01
Morphine hypothermia DRC slope			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		01				Male			-4.58		-7.01		-7.06		-5.75		-6.33		-4.88		-7.36		-2.93				-2.02		-3.43		-3.75		-1.88		-1.31		-4.53						-2.73		-2.12		-5.29		-3.54		-6.06		-5.82		-7.5		-6.06																												-7.65		12/20/2002			MORTEMP		BDTEMP30	Morphine	Dose response across 8, 16, or 32 mg/kg i.p.		JKB	p. 319, Fig 3	MRG 011002; prior confirmation by JKB with data and publication	1632590.01
Morphine analgesia DRC slope			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		02				Male			26.8		59.7		50.1		63.4		30		30.5		62.7		27.6				33.9		25.8		31.2		25.5		36.7		39.1						15.2		10.9		44.3		59.8		35.4		46.3		34.7		24.3																												42.9		12/20/2002			MORHPL8		HOTPLATE	Morphine	Dose response across 8, 16, or 32 mg/kg i.p.		JKB	p. 319, Fig 3	MRG 011002; prior confirmation by JKB with data and publication	1632590.02
Straub tail Morphine DRC slope			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		03				Male			0.94		0.25		1.37		1.04		1.07		0.94		0.42		0.75				0.81		0.94		1.37		0.91		0.73		0.98						0.48		0.61		1.2		0.35		0.75		1.16		1.24		0.75																												0.78		12/20/2002			MORSTRAUB		STRAUB30	Morphine	Dose response across 8, 16, or 32 mg/kg i.p.		JKB	p. 319, Fig 3	MRG 011002; prior confirmation by JKB with data and publication	1632590.03
Saline body temp, degree C			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		04				Male		degrees celsius	37.5		37.7		38.1		37		37.2		38.3		37.4		37.3				38.4		37.8		37.6		36.6		37		38.4						36.8		37.3		37.5		37.5		37.9		38.5		37.8		38.8																												38.2		12/20/2002			SALTEMP		SAL_BTMP	Saline			JKB		MRG 011002; prior confirmation by JKB with data and publication	1632590.04
Saline hot plate latency, seconds			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		05				Male		seconds	20.2		21.3		22		19.5		11.8		8.8		31		18				14.1		11.6		12.8		13		11.9		20						13.8		16.1		12.2		13.5		15		15.5		22.9		9.8																												19.1		12/20/2002			SALHP8		SAL_HOTP	Saline			JKB		MRG 011002; prior confirmation by JKB with data and publication	1632590.05
Saline elevated open field activity, [Unpublished means from same series of studies as reported in:  Belknap & Crabbe, 1992 ANYAS 654:311-323]			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		06				Male			15.44		6.39		9.34		12.15		9.24		15.25		8.4		8.675				14.49		6.43		11.84		7.315		10.25		12.72						7.95		8.3		5.925		6.945		8.26		8.58		5.25		12																														12/20/2002			SALACT(EOF)		SALACT	Saline			JKB		MRG 020402 with JKB	1632590.06
Baseline handling induced convulsions (HIC) 		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet 	23(2)	213-222	Mar	1993		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		01	100 days			Male			0.6995		0.3415		1.6835		2.0565		1.17045		0.3985		1.146		1.8895				0.6495		1.581		1.928		0.1625		0.4835		0.4165						0.7105		0.6315				0.091		0.125		1.5725		0.625		0.0985																														12/20/2002			BASEHIC		AVGAVB				JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.01
Nitrous oxide withdrawal handling induced convulsion (HIC) area under curve		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		02	100 days			Male			5.68		13.24		6.85		1.17		15.6		4.57		5.35		20				2.2		10.15		2.55		1		1.33		3.8						8.87		3.36				6.5		6.67		9		6.94		5.62																														12/20/2002			N2OHIC(AUC)		NCOAUC	Nitrous Oxide	gas 75%	 	JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.02
Corrected peak for nitrous oxide withdrawal handling induced convulsions HIC		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet                                                                                     	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		03	100 days			Male			1.4	0.19	2.94	0.20	1.41	0.25	0.44	0.11	3.4	0.35	1.28	0.27	1.31	0.19	4.17	0.23			0.62	0.19	2.2	0.22	0.88	0.24	0.3	0.13	0.39	0.09	0.73	0.11					2.09	0.36	0.79	0.22			1.71	0.32	1.56	0.28	2	0.31	1.35	0.29	1.35	0.30																													12/20/2002			N2OHIC(PK)		NCORPK2	Nitrous Oxide	gas 75%		JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.03
Nitrous oxide withdrawal handling induced convulsions-difference from baseline (treated minus nontreated)		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet 	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		04	100 days			Male			6.06666666666667		12.635		9.53333333333333		0.333333333333333		14.13		4.25		7.81666666666667		15.977				0.806666666666667		8.35		2.47166666666667		0.55		1.04666666666667		3.55						9.33666666666667		4.24333333333333				6.72666666666667		6.44666666666667		7.21333333333333		9.13666666666667		5.57																														12/20/2002			N2OHIC(DIFF)		NDIFFAUC	Nitrous Oxide	gas 75%		JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.04
Acute ethanol withdrawal-difference from saline,  [Unpublished means from same series of studies as reported in:  Belknap, Metten, Helms, O'Toole, Angeli-Gade, Crabbe & Phillips, 1993 Behav Genetics 23:213-222]		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		05	100 days			Male			5.227		14.08		8.6		9.303		7.9		1.91		3.05		6.27				1.78		5.07		5.6		3.11		6.3		4.06						8.47		5.707				2.21		6.047		6.696		5.5		1.49																														12/20/2002			ETHIC4(DIFF)		DAUC412	EtOH	4 g/kg		JKB		MRG 020402 with JKB	8512534.05
Home cage activity after saline injection		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	01	10-14 wks	70	98	MF	8		13.25		8.375		11.75		8.625		10.75		15.5		11.25		11.375		8.375		7.88888888888889		6		10.75		8		11.875		10.5		12				7.5		11.375		15.75		1.77777777777778		17.125		11.5		7.5		13.5		9.125		8.625		20.75																								6/4/2003	MK Sullivan		SALACT(Home)		ACT0	Saline	Saline	JKBQTL2	JKB	p. 752, Fig 6	MRG 011002 with JKB by publication	8987796.01
Activity-difference from saline for 4 mg/kg methamphetamine [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	02	10-14 wks	70	98	MF	8	quadrant crossings/min	21.625	2.35	18.7678571428571	4.74	47.25	6.70	35.9305555555556	4.39	41.5	7.43	19.25	8.96	7	5.83	33.125	5.26	8.5	2.54	31.8986111111111	3.39	19.875	3.30	13.125	2.96	35.75	6.70	18.125	8.87	21.875	6.26	31.5	6.26			34.375	4.30	9.5	4.74	10.125	5.52	13.8472222222222	4.17	15.5	7.17	22	6.13	25.5	5.39	33.75	4.65	10.375	5.65	30	4.09	14.75	4.09																							6/4/2003	MK Sullivan		MAACT4		DACT4	Meth	4 mg/kg		JKB	p. 748, Fig 2	MRG 011002 with JKB by publication	8987796.02
Activity-difference from saline for 8 mg/kg methamphetamine [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	03	10-14 wks	70	98	MF	8	quadrant crossings/min	11.375	3.61	17	5.61	49.875	7.61	24.4861111111111	4.26	43.125	6.70	1.7	5.04	7.25	4.52	14.25	5.78	6.125	4.87	27.4861111111111	3.73	31.5	1.96	15.25	5.13	16.25	7.78	4.375	2.30	16.5	4.43	26.125	8.52			28.7857142857143	4.13	5.5	3.00	-0.875	3.30	25.3472222222222	5.57	9.375	4.17	40.625	7.65	11.5	4.83	12.125	5.57	23.4305555555556	8.96	37.375	4.78	7.375	3.13																							6/4/2003	MK Sullivan		MAACT8		DACT8	Meth	8 mg/kg		JKB	p. 748, Fig 2	MRG 011002 with JKB by publication	8987796.03
Activity-difference from saline for 16 mg/kg methamphetamine [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	04	10-14 wks	70	98	MF	8	quadrant crossings/min	-8.75	1.89	3.79166666666667	3.96	6.625	9.96	-0.874999999999998	2.39	8.25	4.89	-12.75	1.88	-9.13888888888889	1.14	-2	3.18	-5.75	1.89	-2.88888888888889	3.22	6.875	5.25	3.625	4.89	-7.14285714285714	0.86	-2	3.07	4.875	6.25	-6.85714285714286	1.61			-1.75	2.14	-4.125	3.64	-7.25	2.86	25.4444444444444	4.75	-13.3472222222222	1.64	8	6.75	-1.75	2.46	-7.7	1.57	11.25	3.86	4.25	2.71	-4.25	5.75																							6/4/2003	MK Sullivan		MAACT16		DACT16	Meth	16 mg/kg		JKB	p. 748, Fig 2	MRG 011002 with JKB by publication	8987796.04
Sterotyped chewing responses [N/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	05	10-14 wks	70	98	MF	8	N/min	2.25	0.723	8.375	2.349	0	0.400	1.88888888888889	0.979	1.375	1.396	7.3	1.557	8.25	1.830	5.75	2.323	4.875	1.328	5.04166666666667	2.604	0.125	0.145	2.22222222222222	1.149	9.625	2.162	0.875	0.689	4.5	1.430	7.375	2.545			1.44642857142857	0.987	2.875	2.774	3.375	1.174	1.40277777777778	1.277	0	0.289	3.875	2.026	2.275	1.098	2.125	1.226	0.0833333333333333	0.289	2.125	2.145	-0.125	0.366																							6/4/2003	MK Sullivan		MACHEW8		DCHEW8	Meth	8 mg/kg		JKB	p. 748, Fig 3	MRG 011002 with JKB by publication	8987796.05
Change in body temp due to 4 mg/kg methamphetamine [degree C]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	06	10-14 wks	70	98	MF	8	degree C	0.0124999999999957	0.186	-1.00357142857143	0.536	0.832142857142856	0.345	-0.461111111111116	0.299	0.237500000000004	0.206	-3.72499999999999	0.423	-2.05	0.747	0.424999999999997	0.500	0.0625	0.232	0.588888888888889	0.268	-0.18035714285714	0.232	-1.56250000000001	0.742	0.550000000000004	0.495	-1.2125	0.495	0.362499999999997	0.147	-0.137500000000003	0.711			-1.4375	0.232	-0.487499999999997	0.418	-1.8375	0.820	-1.35277777777779	0.340	-0.275000000000006	0.323	-0.737499999999997	0.325	-1.53750000000001	0.691	-0.537500000000001	0.742	-0.279166666666676	0.299	0.125	0.178	-0.76250000000001	0.289																							6/4/2003	MK Sullivan		MATEMP4		DTEMP4	Meth	4 mg/kg		JKB	p. 747, Fig 1	MRG 011002 with JKB by publication	8987796.06
Change in body temp due to 8 mg/kg methamphetamine [degree C]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	07	10-14 wks	70	98	MF	8	degree C	-0.337499999999991	0.254	-0.0875000000000057	0.207	1.3	0.236	0.294444444444444	0.406	0.674999999999997	0.196	-2.3	0.703	-0.762499999999996	0.283	1.1875	0.120	0.225000000000001	0.330	1.02638888888889	0.232	0.357142857142861	0.286	0.799999999999997	0.351	1.77500000000001	0.196	-1.1125	0.083	1.2375	0.402	0.424999999999997	0.283			0.253571428571433	0.428	0.0124999999999957	0.141	-0.63750000000001	0.630	-0.06527777777778	0.601	-0.125000000000007	0.457	0.525000000000006	0.312	-0.850000000000001	0.580	1.3	0.525	-1.26805555555557	0.359	0.824999999999996	0.170	-0.362500000000004	0.417																							6/4/2003	MK Sullivan		MATEMP8		DTEMP8	Meth	8 mg/kg		JKB	p. 747, Fig 1	MRG 011002 with JKB by publication	8987796.07
Change in body temp due to 16 mg/kg methamphetamine [degree C]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	08	10-14 wks	70	98	MF	8	degree C	0.162500000000001	0.296	0.258333333333326	0.396	1.05	0.217	1.5375	0.316	1.09499999999999	0.316	-0.149999999999991	0.352	0.680555555555557	0.299	1.40000000000001	0.211	0.75	0.316	1.05138888888889	0.228	0.43214285714285	0.168	0.887499999999996	0.177	1.13035714285714	0.493	1.1875	0.524	1.2625	0.382	1.39821428571428	0.234			1.05	0.359	0.325000000000003	0.239	1.1375	0.274	0.377777777777773	0.353	0.791666666666664	0.217	0.725000000000001	0.328	1.2	0.504	2.3525	0.091	-0.100000000000009	0.202	1.2375	0.316	1.01249999999999	0.140																							6/4/2003	MK Sullivan		MATEMP16		DTEMP16	Meth	16 mg/kg		JKB	p. 747, Fig 1	MRG 011002 with JKB by publication	8987796.08
Morphine consumption-two bottle choice [morphine concentration 0.3 to 0.7 mg/ml]		The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		01				Male			157		16		16		42		84		50		27		27				97		29		23		148		16		17						19		96		19		99		52		71		49		97																														12/20/2002			MORCONS		MORCON	Morphine	mg/kg/day		JKB	p. 80, Table 1	MRG 020402 with JKB by publication	2065120.01
Quinine consumption-two bottle choice [quinine concentration 0.1 to 0.4 mg/ml]		The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		02				Male			36		24		32		12		135		20		13		10				11		17		17		62		5		27						11		9		19		58		85		25		39		88																														12/20/2002			QUINCONS		QUINCON	Quinine	mg/kg/day		JKB	p. 80, Table 1	MRG 020402 with JKB by publication	2065120.02
Saccharin preference 	Saccharin preference - mean of 2 studies;Unpublished means from same series of studies as reported in:  1) Phillips, Belknap, Crabbe 1991, J Addictive Diseases 10:73-87;  2) Belknap, Metten, Helms, O'toole, Angeli-Gade, Crabbe & Phillips, 1993 Behav Genetics 23:213-222	The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		97				Male			0.95		0.715		0.79		0.765		0.915		0.9		0.715		0.695				0.765		0.6675		0.805		0.86		0.77		0.765						0.615		0.641		0.84		0.8965		0.717		0.7255		0.873		0.79																														12/19/2002			SACCPREF		SACCPREF	Saccharin	preference ratio		JKB		MRG 020402 with JKB	2065120.97
Saccharin consumption 	Saccharin consumption - mean of 2 studiesUnpublished means from same series of studies as reported in:  1) Phillips, Belknap, Crabbe 1991, J Addictive Diseases 10:73-87;  2) Belknap, Metten, Helms, O'Toole, Angeli-Gade, Crabbe & Phillips, 1993 Behav Genetics 23:213-222	The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		96				Male			806.5		383		352		459.5		1178.5		544.5		342		343				410.5		258.5		528		484		353.5		410						332.5		261.5		417.5		442.5		453.5		365		472		536.5																														12/19/2002			SACCONS		SACCCON	Saccharin	mg/kg/day		JKB		MRG 020402 with JKB	2065120.96
Locomotor activity post cocaine (32 mg/kg) [activity counts/hr]		The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.	Tolliver BK, Belknap JK, Woods WE, Carney JM.	Genetic analysis of sensitization and tolerance to cocaine	J Pharmacol Exp Ther	270(3)	1230-1238	Sep	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7932176&dopt=Abstract	7932176		01				Male	3-8	activitycounts/hr 	1481	89.0	2470	210.3					1814	239.1			2574	251.7			1557	134.3			1622	83.0	1333	69.4	1995	217.4	1787	73.8							2345	83.3	1702	88.7	1383	165.4			2158	112.0	1539	129.6	1494	189.3			1771	117.6	1597	115.8	1909	166.4																							6/26/2003	MK Sullivan		COCACT32		COACT	Cocaine	32 mg/kg		Tolliver/JKB	p. 1235, Fig 6	MRG 011002 with JKB by publication	7932176.01
Sensitization of locomotor response to cocaine (32 mg/kg) [% initial response]		The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.	Tolliver BK, Belknap JK, Woods WE, Carney JM.	Genetic analysis of sensitization and tolerance to cocaine	J Pharmacol Exp Ther	270(3)	1230-1238	Sep	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7932176&dopt=Abstract	7932176		02				Male	3-8	% initial response	81.4		28.2						92.5				71.7				111.4				128.7		97.1		53.1		115.0								59		81.3		100				87.4		86.4		102.0				102		88.6		90																								6/26/2003	MK Sullivan		COCSEN32		COSENSIT	Cocaine	32 mg/kg		Tolliver/JKB	p. 1235, Fig 6	MRG 011002 with JKB by publication	7932176.02
Body weight [g]		Adult C57BL/6J (B6) male mice had 37% heavier brains than did DBA/2J (D2) mice, while their body weights did not differ. The BXD recombinant inbred (RI) series of 20 strains, derived from a cross between B6 and D2 inbred strains, was used as the initial screen to determine significant associations between male brain weight and brain:body weight ratio, with allelic variation at 360 known marker gene loci. For brain weight, this yielded five candidate chromosome regions, each reflecting a possible quantitative trait locus (QTL) site affecting brain weight. The second step was to test as many of these five as possible using standard (non-RI) inbred strain data for brain weight previously reported in the literature. For this purpose, only strains possessing the same alleles as the B6 or D2 strains were used. Sufficient data to test two of the five candidate QTL were available. Of these, one was strongly supported as a site affecting brain weight--the D7rp2 region of chromosome 7. For the brain to body weight ratio, four chromosome regions emerged as significantly associated in the BXD series, but none were amenable to testing due to a lack of allelic information for the standard inbred strains. However, two of these regions showed highly significant associations (p less than 0.001, single test) that merit consideration as QTL sites for future testing. These two are the Hba region on chromosome 11 and the D17Tu7 region on chromosome 17. The genetic correlation between brain and body weight was low (r = 0.28), indicating that these two traits are largely genetically independent in the BXD RI series.	Belknap JK, Phillips TJ, O'Toole LA.	Quantitative trait loci associated with brain weight in the BXD/Ty recombinant inbred mouse strains	Brain Res Bul 	29(3-4)	337-344	Sept-Oct	1992		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1393606&dopt=Abstract	1393606		01	11-13 wks	77	91	Male	7-8	g	25.5	1.71	25.5	2.08	27.6	1.60	28.4	1.84	26.1	1.84	25	2.00	26.4	1.25	27.1	1.64			25.2	0.96	29.3	1.75	30.4	1.60	27.8	1.54	26.75	1.91	29	2.56					28.4	3.26	25.1	0.79	24.3	2.42	25	1.66	24.7	2.17	25.2	2.06	26.3	1.83	24.7	2.23																													6/24/2003	MK Sullivan		BODYWGT		BODWGT			BODYWGT	JKB	p. 340, Table 1	MRG 011002 with JKB by publication	1393606.01
Brain weight [mg]		Adult C57BL/6J (B6) male mice had 37% heavier brains than did DBA/2J (D2) mice, while their body weights did not differ. The BXD recombinant inbred (RI) series of 20 strains, derived from a cross between B6 and D2 inbred strains, was used as the initial screen to determine significant associations between male brain weight and brain:body weight ratio, with allelic variation at 360 known marker gene loci. For brain weight, this yielded five candidate chromosome regions, each reflecting a possible quantitative trait locus (QTL) site affecting brain weight. The second step was to test as many of these five as possible using standard (non-RI) inbred strain data for brain weight previously reported in the literature. For this purpose, only strains possessing the same alleles as the B6 or D2 strains were used. Sufficient data to test two of the five candidate QTL were available. Of these, one was strongly supported as a site affecting brain weight--the D7rp2 region of chromosome 7. For the brain to body weight ratio, four chromosome regions emerged as significantly associated in the BXD series, but none were amenable to testing due to a lack of allelic information for the standard inbred strains. However, two of these regions showed highly significant associations (p less than 0.001, single test) that merit consideration as QTL sites for future testing. These two are the Hba region on chromosome 11 and the D17Tu7 region on chromosome 17. The genetic correlation between brain and body weight was low (r = 0.28), indicating that these two traits are largely genetically independent in the BXD RI series.	Belknap JK, Phillips TJ, O'Toole LA.	Quantitative trait loci associated with brain weight in the BXD/Ty recombinant inbred mouse strains	Brain Res Bul 	29(3-4)	337-344	Sept-Oct	1992		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1393606&dopt=Abstract	1393606		02	11-13 wks	77	91	Male	7-8	mg	465	23	339	19	450	22	390	19	477	27	361	16	421	13	419	15			412	13	403	9	439	9	429	14	436	16	427	13					409	20	431	10	432	30	380	17	394	16	381	18	389	20	375	11																													6/24/2003	MK Sullivan		BRAINWGT		BRAINWGT			BRAINWGT	JKB	p. 340, Table 1	MRG 011002 with JKB by publication	1393606.02
Cocaine in mg/kg (infused via tail vein) to   induce tonic seizure  [mg/kg]		Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F(2) population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F(2) population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F(2) results, three QTLs emerged as significant (P <.00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P <.0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males.	Hain HS, Crabbe JC,       Bergeson SE, Belknap JK. 	Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains	J Pharmacol Exp Ther	293(1)	180-187	Apr	2000		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10734168&dopt=Abstract	10734168		01	56-100 days 	56	100	Female	7-16	mg/kg	36.5092843340253	1.05	45.8623787362414	1.15	42.9703626911218	1.99	46.3609349736889	1.81	43.4960099553144	3.05	48.0771280463759	2.93	44.6149206926665	2.06	38.9730137289765	1.64	48.6677557555129	1.60	39.5212449334861	1.03	39.4036744928305	1.27	39.9767680020278	1.74	37.3012008962622	1.55	43.3300328369933	1.78	39.4037704331372	1.18	45.4332262655791	1.24			35.9427625388382	1.01	49.5509290179926	2.94			38.7927845701966	1.48	46.6208980595439	3.05	38.7701207182665	1.08	38.7466553026451	1.64	44.3891465498985	2.56	42.0057332089545	1.24	34.0522375511561	0.70	44.0018244149537	1.59																							6/4/2003	MK Sullivan	MK Sullivan	COCTON		MGKGTON	Cocaine	1mg/ml	RI-166	JKB/JCC	p. 182, Fig.1 top	JD 121301  from publication	10734168.01
Cocaine in mg/kg (infused via tail vein) to induce clonic seizure [mg/kg]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            		Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F(2) population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F(2) population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F(2) results, three QTLs emerged as significant (P <.00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P <.0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males.	Hain HS, Crabbe JC,  Bergeson SE, Belknap JK. 	Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains	J Pharmacol Exp Ther	293(1)	180-187	Apr	2000		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10734168&dopt=Abstract	10734168		02	56-100 days 	56	100	Female	7-16	mg/kg	21.1275869781027	0.75	21.903677521797	1.59	24.3794503374416	3.26	21.8333066738383	2.18	21.6786293001535	2.46	20.1582397852819	1.24	23.9731186492713	1.45	21.8606255012244	1.83	24.867635937228	1.55	17.5034216551746	1.22	21.7689514914138	0.99	21.8178716923466	1.76	17.4457084496112	1.71	20.1131869961416	1.18	24.3516411928639	1.45	23.4871948042632	1.45			20.3500609275227	1.01	23.5815221713196	2.51			20.7144960755053	1.72	22.1648480352814	2.23	22.8863072036995	1.95	19.6430463704733	1.43	20.8623671215829	1.66	22.8056520761417	1.66	20.1509430417039	1.20	20.7370448138035	0.98																							6/4/2003	MK Sullivan	MK Sullivan           	COCCLO		MGKGCLO	Cocaine	1mg/ml	RI-166	JKB/JCC	p. 182, Fig.1 bottom	JD 121301  from publication	10734168.02
Acute ethanol activity response - Difference between experimental 2g/kg ip EtOH and saline control group [activity counts/min]		Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL 	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	01	56-125 days	56	125	Male	13-34	activity counts/min	28.869	8.34	75.200	8.27	42.207	8.30	20.144	4.90	36.412	2.44	15.49	3.92	85.832	4.97	49.069	4.57	52.4	6.92	2.147	4.90	43.093	4.50	58.071	6.34	18.172	2.91	15.048	2.78	44.434	7.15					50.538	5.53	33.052	5.00			28.221	3.84	68.007	9.87	38.566	10.60	23.353	4.77	31.488	5.05																													7/3/2003	MK Sullivan		ETSALACT(C1DIFF)	Figure 1 data; also EtOH: Act in Tables 4-5	E1MS1; C1	EtOH	2 g/kg	CPP-59	CLC	Fig 1; Tables 4-5	MRG 120601 from publication	7480533.01
Within-subject tolerance/sensitization to ethanol effects on locomotor activity (i.e., 4th ethanol trial activity minus 1st ethanol trial activity)		Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology 	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	02	56-125 days	56	125	Male			-59.094		26.921		-44.237		-26.048		-22.375		-47.387		-10.206		15.869		-37.031		-23.027		-19.28		-30.107		-15.159		-29.042		-1.931						10.117		-2.704				7.3		-34.855		34.772		-15.973		-4.218																														12/20/2002			ETSEN (C4C1)	SENS1: ACT	E4ME1	EtOH	2 g/kg	CPP-59	CLC	means not in paper; analyzed in Tables 4-5	MRG 120601 from publication	7480533.02
Ethanol induced conditioned place preference - Time on EtOH paired floor during 30 min test [%]		Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL 	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	03	56-125 days	56	125	Male	6-16	%	58.316	2.38	59.618	3.38	65.087	3.56	62.43	3.56	54.588	2.58	63.214	2.80	59.001	2.26	60.163	2.01	78.344	3.80	57.973	2.87	59.701	2.74	55.239	2.54	64.039	2.92	61.564	5.14	57.696	1.98					49.491	1.80	65.529	5.04			74.6	3.32	49.865	2.18	66.859	4.08	54.526	3.50	53.349	1.99																													7/2/2003	MK Sullivan		ETCPP	PREF	PDT30	EtOH	2 g/kg	CPP-59	CLC	p. 33, Fig 2	JD 010302 from publication	7480533.03
Within-subject habituation (i.e., 4th saline trial activity minus 1st saline activity trial activity)	[Unpublished means from same series of studies as reported in:    Cunningham 1995 PsychoPharm 120:28-41]	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	95	56-125 days	56	125	Male			-47.925		-10.243		-37.8		-36.568		-13.088		-41.865		-18.465		-20.793		-21.569		-32.167		-22.473		-23.9		-8.386		-17.503		-14.676						-6.034		-11.252				-6.357		-32.848		-26.041		-14.067		-18.888																														12/19/2002			SALACT(C4C1)		S4MS1	Saline		CPP-59	CLC		JD 010302 from publication	7480533.95
Acute Locomotor Activity Response to 2 g/kg i.p. EtOH on 11th day in chronic saline injected mice, 1- 5 minutes after injection [cm]		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	01	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	546		973		-241		725		-208		-493		1185		358		921		387		662		813		-266		38		726						1074		454		996		194		1242		837		529		309																														12/27/2002			ETACT2(CS)	ACCS	CS5D11D2	EtOH	2 g/kg	RI-58	TJP	Figure 1 inset y-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.01
Ethanol Locomotor Sensitization Between Group: Acute Response to 2 g/kg EtOH, Day 11 Locomotor Activity Difference (Chronic EtOH minus Chronic Saline), 1-5 minutes after injection [cm] 		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	02	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	-694		-134		-468		507		435		395		-558		663		456		-372		1226		275		176		1026		1065						696		-62		758		935		430		388		677		356																														12/27/2002			ETSEN2(BG)	deltaBG	BGSENS5M	EtOH	2 g/kg	RI-58	TJP	Figure 2 inset y-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.02
Ethanol Locomotor Sensitization Within Group: Change in locomotor response, 1 - 5 minutes after 2 g/kg EtOH injection (i.p) after repeated treatment; Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) for the chronic EtOH group [cm]		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	03	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	-318	124	-725	350	-866	200	260	289	279	117	-51	223	-1013	488	1060	303	726	492	-297	303	644	309	-46	231	365	188	433	242	1119	309					682	427	39	242	1125	293	899	175	252	203	402	270	586	298	192	266																													7/2/2003	MK Sullivan		ETSEN2(CD)	deltaCD	D11D35M	EtOH	2 g/kg	RI-58	TJP	Figure 2 and Figure 2 inset x-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.03
Acute locomotor response, 1 to 5 minutes after 2g/kg i.p. EtOH in chronic ethanol sensitized mice [cm] 		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	04	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	84	114	1521	263	268	265	843	100	-174	95	-36	138	1587	358	-162	174	924	396	504	168	976	200	1157	243	-204	121	649	159	675	187					1026	284	163	124	644	210	45	87	1445	189	891	181	747	193	382	143																													7/2/2003	MK Sullivan		ETACT2(CD)	ACCD	D3D25M	EtOH	2 g/kg	RI-58	TJP	Figure 1 and Figure 1 inset x-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.04
Locomotor Activity Day 2, 1 - 5 minutes after saline i.p. [cm]		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	05	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	1447		1362		1661		1528		1086		1162		886		1845		573		1643		1175		1729		1171		1035		2014						1411		949		1264		823		1360		1074		899		2146																														12/27/2002			SALACT(5MIN)	BASACT5	SAL5M	Saline		RI-58	TJP	Basis for QTL analysis of basal activity, p. 272 Table 2	MRG 010202 with TJP from publication and data file	7625557.05
Consumption of 0.2% saccharin (mg/kg) vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		01	51-125 days	51	125	Female	10-18	g/kg/day	853.935	111.717	471.707	73.838			250.743	80.303	748.408	168.939	787.394	43.939			330.42	58.485			343.077	57.980	420.033	54.495	537.171	90.909	652.835	72.576	415.414	47.879	412.785	59.596	639.584	75.253			533.912	23.333			438.621	105.001	674.217	92.980	807.822	70.152	534.837	58.434			1071.038	88.637			591.661	116.768	572.167	55.012																							7/11/2003	MK Sullivan		SACCONS0.2(%)	0.2%SacCon	AVSACCON	Saccharin	0.002	RI-72	TJP	p. 935, Fig. 2	MRG 010202 with TJP from publication and data file	7978106.01
Consumption of 3% Ethanol (g/kg) vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		02	51-125 days	51	125	Female	10-18	g/kg/day	3.538	0.557	0.279	0.264			2.052	0.841	1.669	0.734	2.086	0.417			0.981	0.301			2.765	0.446	0.438	0.286	0.906	0.374	3.578	0.657	2.218	0.539	0.951	0.341	2.975	0.403			0.967	0.516			1.64	0.786	0.614	0.246	1.741	0.551	2.159	0.821			2.795	0.517			2.658	0.601	0.819	0.429																							7/11/2003	MK Sullivan		ETCONS3(%)	3%EtOHCon	AV3EG	EtOH	0.03	RI-72	TJP	p. 934, Fig.1	MRG 010202 with TJP from publication and data file	7978106.02
Consumption of 3% Ethanol (g/kg) in 0.2% saccharin vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		03	51-125 days	51	125	Female	10-18	g/kg/day	10.965	0.635	2.000	0.721			6.135	0.833	11.207	1.051	7.023	0.829			2.924	0.633			4.828	0.424	6.245	1.666	6.159	0.945	7.236	0.875	5.58	0.563	3.274	0.845	5.534	0.614			5.473	0.547			11.658	0.719	6.992	0.630	8.083	0.547	6.646	0.766			10.266	0.896			7.308	1.060	4.638	0.980																							7/11/2003	MK Sullivan		ETSACCONS3(%)	3%EtOH/SacCon	AV3SG	EtOH	0.03	RI-72	TJP	p. 935, Fig. 2	MRG 010202 with TJP from publication and data file	7978106.03
Consumption of 10% Ethanol (g/kg) in tap water offered vs. tap water; means are the average of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		04	51-125 days	51	125	Female	10-18	g/kg/day	10.562	1.319	1.306	0.981			6.084	1.505	5.506	1.192	4.425	1.008			0.601	0.012			2.759	0.918	0.687	0.411	1.741	0.613	5.836	1.210	4.849	1.407	0.364	0.105	2.477	0.916			2.589	1.017			2.203	1.032	2.417	0.805	2.024	0.706	6.658	0.903			2.466	0.901			8.096	1.403	1.28	0.905																							7/11/2003	MK Sullivan		ETCONS10(%)	10%EtOHCon	AV10EG	EtOH	0.1	RI-72	TJP	p. 934, Fig.1	MRG 010202 with TJP from publication and data file	7978106.04
Consumption of 10% Ethanol (g/kg) in 0.2% saccharin and tap water offered vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		05	51-125 days	51	125	Female	10-18	g/kg/day	18.194	1.847	1.05	0.660			11.378	1.216	13.58	1.435	12.161	1.241			1.98	0.637			6.256	1.020	6.588	2.212	5.727	1.120	14.376	0.540	11.1	1.626	3.678	1.112	6.692	1.543			8.083	1.528			15.58	1.78	10.256	0.747	10.05	0.235	12.975	1.642			13.02	1.740			12.737	0.871	4.135	1.568																							7/11/2003	MK Sullivan		ETSACCONS10(%)	10%EtOH/SacCon	AV10SG	EtOH	0.1	RI-72	TJP	p. 935, Fig. 2	MRG 010202 with TJP from publication and data file	7978106.05
Corrected area under the Ethanol withdrawal curve; mice were assessed for handling-induced convulsions after voluntary ethanol consumption.		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		06	51-125 days	51	125	Female	10-18		5.66		2.61				0.52		2.18		5.69				0.6				1.64		1.05		1.17		3.21		4.68		0.48		0				4.82				1.26		1.75		2.33		3.3				3.42				0.31		1.5																								12/20/2002			ETHIC	EtOHWD	COAUC	EtOH	0.1	RI-72	TJP	p.938, Table 2	MRG 010202 with TJP from publication and data file	7978106.06
Preference for 10% Ethanol (g/kg) in tap water offered vs. tap water; means are the average of days 2 and 4 of a 4-day 24-hr access period.		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		07	51-125 days	51	125	Female	10-18		0.554		0.086				0.32		0.35		0.251				0.051				0.168		0.045		0.061		0.356		0.302		0.024		0.167				0.146				0.127		0.265		0.171		0.428				0.14				0.488		0.112																								12/20/2002			ETPREF10(%)	10%EtOHPref	PR10E	EtOH	0.1	RI-72	TJP	p. 934, Fig.1	MRG 010202 with TJP from publication and data file	7978106.07
Locomotor response (photocell beam interruptions) to acute 2 g/kg i.p Ethanol injection; Day 3 (first Ethanol treatment) minus Day 2 (saline baseline) in the chronic EtOH group; 10 min activity test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR. 	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		01				Female			-18		151		96		350		-227		-401		88				188		-128		353		79		78		-67		269		541				562		-117		-37		-44		241		608		-23		58		947		-142		-345																								12/20/2002			ETACT2(GRIDCD)		ACTD3D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 2 top	MRG 010202 with TJP from publication and data file	8627538.01
Locomotor response (photocell beam interruptions) to acute 2 g/kg Ethanol injection (i.p); Day 11 (only Ethanol treatment) minus Day 2 (saline baseline) in the chronic saline (CS) group; 10 min activity test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		02				Female			-105		272		68		304		-426		-443		170				262		33		524		-68		3		-214		213		780				428		8		-23		79		247		687		-30		538		979		-13		-379																								12/20/2002			ETACT2(GRIDCS)		ACTD11D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 2 top inset	MRG 010202 with TJP from publication and data file	8627538.02
Change in locomotor response (photocell beam interruptions) to 2 g/kg i.p EtOH injection (i.p) after repeated treatment; Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) in the chronic drug (CD) group; 10 min activity test (Grid test inside Accuscan activity monitors).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther2	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		03				Female			20		265		164		-238		254		214		121				395		201		516		119		210		386		482		234				136		234		360		98		548		-140		428		982		261		205		466																								12/20/2002			ETSENS2(GRIDCD)		ACTD11D3	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 2 bottom	MRG 010202 with TJP from publication and data file	8627538.03
Acute Ethanol Ataxia: Grid test errors after acute 2 g/kg EtOH injection (i.p); Day 3 (first EtOH treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		04				Female			114		123		135		187		86		103		143				129		154		191		165		138		227		320		289				186		108		165		132		151		185		152		298		159		164		109																								12/20/2002			ETGRID2(CD)		ERRD3D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 1 top	MRG 010202 with TJP from publication and data file	8627538.04
Acute Ethanol Ataxia: Grid test errors after acute 2 g/kg EtOH injection (i.p); Day 11 (only EtOH treatment) minus Day 2 (saline baseline) in the chronic saline (CS) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		05				Female			116		168		150		199		91		111		201				153		140		230		210		129		195		287		351				175		110		185		106		172		256		130		337		212		171		107																								12/20/2002			ETGRID2(CS)		ERRD11D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 1 top inset	MRG 010202 with TJP from publication and data file	8627538.05
Change in misstep errors induced by repeated 2 g/kg EtOH injection (i.p); Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) in the chronic drug (CD) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		06				Female			-33		-40		33		-83		-13		-14		-18				-43		-40		64		-5		-13		-30		83		-34				-33		-10		-8		-69		-7		4		66		-63		-57		-24		47																								12/20/2002			ETGRIDTOL2(CD)		ERRD11D3	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 1 bottom	MRG 010202 with TJP from publication and data file	8627538.06
Ataxia ratio (errors/activity counts) in the Grid test after acute 2 g/kg Ethanol injection (i.p); Day 3 (first Ethanol treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; 10 min test (Grid test inside Accuscan activity monitors).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		07				Female			17.6		11.4		14.8		20.8		18.1		25.2		18.5				14.9		17.6		18		19.7		17.7		47.6		26.4		22.9				14.5		19.8		26.3		33.7		14		14.3		24.4		16.9		9		29.9		24																								12/20/2002			ETGRID2 (CD RATIO)		RATD3D2	EtOH	2 g/kg	RI-82	TJP	p. 617, Fig 3 top	MRG 010202 with TJP from publication and data file	8627538.07
Ataxia ratio (errors/activity counts) in the Grid test after acute 2 g/kg Ethanol injection (i.p); Day 11 (only EtOH treatment) minus Day 2 (saline baseline) in the chronic saline (CS) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		08				Female			15.9		14.7		14.3		19.9		26		27.5		22.7				18.2		15.1		18.1		26		17.5		47.5		24.5		24.5				16.1		17.4		27.3		27.1		17.9		18.5		22.1		17.6		11.1		32.7		22.9																								12/20/2002			ETGRID2 (CS RATIO)		RATD11D2	EtOH	2 g/kg	RI-82	TJP	p. 617, Fig 3 top inset	MRG 010202 with TJP from publication and data file	8627538.08
Change in ataxic effects of 2 g/kg Ethanol injection (i.p) after repeated treatment; Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) in the chronic drug (CD) group; 10 min test (Grid test inside Accuscan activity monitors).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		09				Female			-6.9		-5.1		0.3		-8		-6.8		-11.2		-2.8				-8		-8.2		-1.3		-5.4		-5.3		-23.5		-0.6		-5.3				-3.8		-8.4		-10.2		-22.3		-5.8		0.8		-2.7		-8.6		-4.6		-12.4		-7.5																								12/20/2002			ETGRIDTOL2 (CD RATIO)		RATD11D3	EtOH	2 g/kg	RI-82	TJP	p. 617, Fig 3 bottom	MRG 010202 with TJP from publication and data file	8627538.09
Baseline locomotor activity measured in the grid test (photocell beam interruptions); activity on the second day (Day 2) of exposure to the testing procedure after saline injection (i.p); 10 min activity test (Accuscan Activity Monitor Grid test).	[data from all mice, regardless of subsequent treatment designation, are included in the calculation of these means.]	Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		10				Female			825		877		975		795		756		873		705				641		1040		725		971		766		621		967		762				721		700		790		510		813		762		645		1596		814		693		887																								12/20/2002			SALACT(GRID10MIN)		TACTD2	Saline	0.009	RI-82	TJP	Tables 2, 3, 4, 5	MRG 010202 with TJP from publication and data file	8627538.1
Baseline locomotor activity (distance traveled); indexed as activity on the second day (Day 2) of exposure to the activity testing procedure after saline injection (ip); strain means are for a 15 min activity test (Accuscan activity monitors); data from all mice, regardless of subsequent treatment designation, are included in the calculation of these means [cm]		Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		01	52-131 days	52	131	Female	7-13	cm	2826.817	83	2799.718	112	3664.41	206	2743.583	88	2678.948	450	2617.875	125	2099.213	31	4694.203	144	1362.016	56	3449.317	111	2847.36	103	3622.441	100	3085.517	137	1983.133	159	4519.183	147	3043.587	275			2886.951	69	2093.051	147	2820.622	133	1630.075	108	2906.806	116	2545.333	147	1674.5	94	5521.39	194	3115.333	88	2654.052	127	3486.719	107																							6/4/2003	MK Sullivan		SALACT(15MIN)	BASACT	BASED2	Saline	0.9% or 10 ml/kg	RI-86	TJP	p. 3026, Fig 1 inset.	MRG 121301 by Fig 1 inset, p. 3026 Basal Activity	9526019.01
Locomotor response (distance traveled) to an acute 5 mg/kg cocaine injection (ip); indexed as Day 3 (first cocaine treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; strain means are for a 15 min activity test (Accuscan activity monitors) [cm]		Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		94	52-131 days	52	131	Female	7-13	cm	1297.667	118	2004	261	2726.25	632	2301	211	412.6	253	4.692	43	1229.417	85	3147.417	396	-468.417	0	1689.25	329	1944.4	211	2009.083	337	916.25	144	52.385	177	3776.455	674	2880.231	76			2212.25	539	745.5	0	1521.429	0	-139.818	0	1853.667	716	141.385	144	1411.231	286	571.364	505	1223.25	573	1440.364	808	317.6	640																							6/4/2003	MK Sullivan		COCACT5(CD)	ACCD5	COCAC5	Cocaine	5 mg/kg	RI-86	TJP	p. 3026, Fig 1   bottom.     	JD 121301  from file	9526019.94
Locomotor response (distance traveled) to an acute 10 mg/kg cocaine injection (ip); indexed as Day 3 (first cocaine treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; strain means are for a 15 min activity test (Accuscan activity monitors) [cm]		Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		02	52-131 days	52	131	Female	7-13	cm	2961.25	690	3386.929	782	8506.818	1261	4132.167	817	3241	652	3306.25	730	3463.417	913	5637.167	843	1755.692	817	7339	1252	3957.9	565	3418.667	548	3078.091	904	99.667	357	5716.333	791	7159.5	1261			5805.083	1122	5342.25	1504	5091.125	957	1101.545	604	4192.417	877	4569.417	1608	2988.667	609	3540.615	939	5187.231	635	4367.273	565	5093.091	1043																							6/4/2003	MK Sullivan		COCACT10(CD)	ACCD10	COCAC10	Cocaine	10 mg/kg	RI-86	TJP	p. 3026, Fig 1  top.     	JD 121301  from file	9526019.02
Locomotor response (distance traveled) to an acute 40 mg/kg cocaine injection (ip); indexed as Day 3 (first cocaine treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; strain means are for a 15 min activity test (Accuscan activity monitors) [cm]		Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		03	52-131 days	52	131	Female	7-13	cm	12932.833	758	12608.867	1238	15426.923	1592	14007.667	994	4837	733	12578.385	935	8107.417	1684	13238.75	1238	7105.692	1322	10082.538	1297	7614.1	893	8616.091	775	6817.5	1347	5307.417	1288	12385.667	935	14297.75	1625			10363.333	931	12060.889	1709	13099.286	3671	2832.9	707	7053	1263	14651.727	1120	10958.462	1625	11884.25	1213	8294.154	1811	15252.917	640	10339.917	1432																							6/4/2003	MK Sullivan		COCACT40(CD)	ACCD40	COCAC40	Cocaine	40 mg/kg	RI-86	TJP	p. 3026, Fig 1   bottom.     	JD 121301  from file	9526019.03
Cocaine induced sensitization of locomotor response (distance traveled) to 5 daily 5 mg/kg cocaine injections (i.p); Day 11 (fifth cocaine treatment) minus Day 3 (first cocaine treatment); 15 min activity test (Accuscan activity monitors) [cm]	[NOTE:  Highlighted mean was reported incorrectly in the cited publication; it is correct in this table.  All QTL analyses and genetic correlations were reported correctly in the cited publication:   'Phillips, Huson, McKinnon, 1998 JNeurosci 18: 3023-3034]	Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		93	52-131 days	52	131	Female	7-13	cm	3395.417	839	3456.857	779	3015.25	1940	1590	854	1287.444	742	1901.923	667	1616.5	419	3988.667	719	1729.25	816	1232.5	779	2971.5	382	1963.636	479	644.25	547	1597.231	577	630.455	903	3115.231	188			1851.833	921	1931.125	1258	3096.714	816	1753.182	442	2246.25	861	4200.308	995	3825.538	1131	1217.455	841	3591.333	839	1692.818	712	4256.778	779																							6/4/2003	MK Sullivan		COCSEN5(CD)	deltaCD5	COCSEN5	Cocaine	5 mg/kg	RI-86	TJP	p.3027, Fig 2	JD 121301  from publication	9526019.93
Cocaine induced sensitization of locomotor response (distance traveled) to 5 daily 10 mg/kg cocaine injections(ip); indexed as Day 11 (fifth cocaine treatment) minus Day 3 (first cocaine treatment); 15 min activity test (Accuscan activity monitors) [cm]		Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		04	52-131 days	52	131	Female	7-13	cm	3823	839	4570.714	644	6091.364	2548	2503.727	1030	3704.727	1184	6180	951	2812.917	1487	4479.333	1294	1517.231	1040	1760.833	1110	4708	925	3883.5	782	3864.5	1026	893.083	419	3789	921	8423.75	653			5866.083	1041	4600	2382	2285.5	1086	2925.818	404	4008.583	1491	5286.583	2494	4198.75	1139	-1518.923	1108	2158	1169	3725.273	813	4234.818	1063																							6/4/2003	MK Sullivan		COCSEN10(CD)	deltaCD10	COCSEN10	Cocaine	10 mg/kg	RI-86	TJP	p.3027, Fig 2	JD 121301  from publication	9526019.04
Cocaine induced sensitization of locomotor response (distance traveled) to 5 daily 40 mg/kg cocaine injections (ip); indexed as Day 11 (fifth cocaine treatment) minus Day 3 (first cocaine treatment) distance traveled (in cm);  15 min activity test (Accuscan activity monitors) [cm]	 	Sensitization to the psychostimulant effects of cocaine has received widespread attention because concomitant changes occur in neurochemical pathways that are part of the brain reward pathway. The current study was undertaken with the purpose of mapping genes determining sensitivity to the acute stimulant and sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10, and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13, 18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There were both common and unique QTL regions across the phenotypes. Evidence for a genetic association between magnitude of acute cocaine response and sensitization was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine, ethanol, and methamphetamine responses suggest the possibility that these drugs induce stimulant effects or sensitization through some common mechanisms. However, independent mechanisms were also indicated. Many candidate genes reside near the provisional QTLs mapped for cocaine responses, including genes coding a variety of neurotransmitter and hormone receptors. These data, once confirmed, should prove useful for directing investigations of acute and chronic cocaine effects down already suspected and novel avenues.	Phillips TJ, Huson MG, McKinnon CS.	Localization of genes mediating acute and sensitized locomotor responses to cocaine in BXD/Ty recombinant inbred mice	J Neurosci 	18(8)	3023-3034	Apr	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9526019&dopt=Abstract	9526019		05	52-131 days	52	131	Female	7-13	cm	-1069.333	1367	1470.4	1709	5966.538	2300	-2287.75	1441	4268.083	1252	1017.154	1108	3505.167	1929	2721.333	2071	872.615	1940	-4245.615	1650	7010.8	1476	993.364	1175	471.5	2017	3670.333	2127	3281.25	1976	5300.333	2182			3580.833	1086	-2874.444	2408	2053.143	5161	4624.7	1236	-2123.308	1700	-3130.7	1805	2830.692	1536	-283.833	1124	4110.538	2840	2393.417	1022	3420.25	2060																							6/4/2003	MK Sullivan		COCSEN40(CD)	deltaCD40	COCSEN40	Cocaine	40 mg/kg	RI-86	TJP	p.3027, Fig 2	JD 121301  from publication	9526019.05
Locomotor response (distance traveled in cm) to 20% 2-hydroxypropyl-beta-cyclodextrin vehicle injection (ip); indexed as Day 3 (third vehicle treatment) minus Day 2 (vehicle baseline) in the vehicle control group; strain means are for a 30 min activity test (Accuscan activity monitors).		Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes.	Palmer AA, Miller MN, McKinnon CS, Phillips TJ	Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes	Behav Neurosci 	116(1)	126-137	Feb	2002 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11895174&dopt=Abstract	11895174		01	50-123 days	50	123	Female	10-27	cm	-88.04762268	479.78	-640.5999756	319.13	-321.125	416.39	-1170.300049	159.02	-1008.166687	412.57	-1589.119995	461.75	-174.1538391	278.69	-816	798.09	-483.9285583	300.01	-923.833313	274.59	-25.81818199	366.12	-1479.083374	300.02	-1180.153809	805.46	-207.9166718	551.37	-535.6153564	560.38	276.0666809	327.32			-408.7692261	456.56	-408.6923218	284.70			-204.5	415.85	-1464.230713	289.62	285.2142944	356.56	-521.4615479	260.11	-1958.199951	566.12	-312.615387	294.54	-524.4615479	258.20	-620.2272949	358.47																							6/23/2003	MK Sullivan		VEHACT(30MIN)		ALLO-0	Allopregnanolone	0mg/kg	RI-163	TJP/AAP	p.129, Fig 1	MRG and AAP 02/06/02	11895174.01
Locomotor response (distance traveled in cm) to 10 mg/kg allopregnanolone (3a-hydroxy-5a-pregnan-20-one, THP) in 20% 2-hydroxypropyl-beta-cyclodextrin vehicle injection (ip); indexed as Day 3 (first allopregnanolone treatment) minus Day 2 (vehicle baseline); strain means are for a 30 min activity test (Accuscan activity monitors).		Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes.	Palmer AA, Miller MN, McKinnon CS, Phillips TJ	Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes	Behav Neurosci 	116(1)	126-137	Feb	2002 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11895174&dopt=Abstract	11895174		02	50-123 days	50	123	Female	10-27	cm	3477.600098	805.79	3019.899902	519.83	598.4666748	781.82	2017.666626	730.58	846.3076782	785.08	1093.136353	445.45	1020	379.34	1203.588257	1160.33	674	549.59	1166.058838	702.48	1419.272705	495.45	1484.75	644.63	1831.769287	645.04	3109.764648	1121.90	1081.692261	533.88	2940.642822	752.89			994.916687	772.31	1652.583374	479.34			337.0909119	523.97	523.6923218	582.64	801.7142944	353.72	1036.230713	379.34	1559	873.97	11	398.76	393.6666565	355.79	694.458313	534.30																							6/23/2003	MK Sullivan		ALLOACT10		ALLO-10	Allopregnanolone	10mg/kg	RI-163	TJP/AAP	p.129, Fig 1	MRG and AAP 02/06/02	11895174.02
Locomotor response (distance traveled in cm) to 17 mg/kg allopregnanolone (3a-hydroxy-5a-pregnan-20-one) in 20% 2-hydroxypropyl-beta-cyclodextrin vehicle injection (ip); indexed as Day 3 (first allopregnanolone treatment) minus Day 2 (vehicle baseline); strain means are for a 30 min activity test (Accuscan activity monitors).		Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes.	Palmer AA, Miller MN, McKinnon CS, Phillips TJ	Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes	Behav Neurosci 	116(1)	126-137	Feb	2002 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11895174&dopt=Abstract	11895174		03	50-123 days	50	123	Female	10-27	cm	2414.730703	681.74	5722.411621	908.71	2639.666748	1427.39	4524.90918	1020.75	2317.923096	732.37	3171.173828	763.49	3867.769287	945.64	3759.9375	1386.72	4051	1248.13	3099.882324	598.34	2904.916748	900.03	2294.166748	924.90	3454.230713	743.57	4645.222168	1361.00	5758.307617	1327.80	5285.5	1641.08			4636.692383	1079.67	3529.083252	788.38			3781	1045.64	4282.143066	1526.97	6489.571289	1573.44	428.1666565	542.74	5010.5	1568.46	6124.307617	1369.71	2913.083252	968.46	4020.407471	622.41																							6/23/2003	MK Sullivan		ALLOACT17		ALLO-17	Allopregnanolone	17mg/kg	RI-163	TJP/AAP	p.129, Fig 1	MRG and AAP 02/06/02	11895174.03
Ethanol acceptance - Ratio relative to water (within mouse)	Alcohol Acceptance Ratio; ratio of ethanol intake (ml) on test day to average water intake (ml) measured on first two days	Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		01				Male			0.75		0.29		0.44				1.09		0.07		0.53				0.67		0.67				0.34		0.49		0.73				0.66				0.5				0.82		0.44		0.08				0.04		0.63		0.18																												12/20/2002			ETACC10	ACCRATIO	ACCRATIO	EtOH	10% EtOH		JCC	p. 184, Table 2	JD 020502  from publication	6683363.01
Ethanol acceptance - Total ethanol intake [g/kg]		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		02				Male			12.6		3.36		3.52				9.95		1.32		10.89				13.34		8.9				8.29		7.65		9.34				10.21				12.66				10.78		2.43		1.03				0.68		4.81		2.34																												12/20/2002			ETCONS10	ETINTAKE	ETINTAKE	EtOH	10% EtOH    ( v/v)		JCC	p. 184, Table 2	MRG 120601 from publication	6683363.02
Saline open Field Activity - beam interruptions after saline administration		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		03				Male			155		132		175		182		240		152		113				79		141		127		152		104		158		131		166				171				159		125				134		89		171		95																												12/20/2002			SALACT	OFA	OFACTIV	Saline			JCC	p. 184, Table 1	MRG 120601 from publication	6683363.03
Ethanol open field activity - beam interruptions after EtOH administration		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		04				Male			83		335		264		155		178		144		171				133		317		121		245		117		252		150		268				251				204		154				187		170		226		233																												12/20/2002			ACT1.3	ETOFA	ETACTIV	EtOH	1.33 g/kg		JCC	p. 184, Table 1	JD 020502  from publication	6683363.04
Ethanol open field activity - difference relative to saline	EtOH Effect on Open field activity. Activity (beam interruptions) in 4 min (day 2 - day 1) or (ETOFA - OFA)	Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		05				Male			-72		203		89		-27		-62		-8		58				54		176		-6		93		13		94		19		102				80				45		29				53		81		55		138																												12/20/2002			ETACT1.33(delta)	ACT	ETDELTOF	EtOH	1.33 g/kg		JCC	p. 184, Table 1	MRG 120601 from publication	6683363.05
Ethanol induced ataxia, Errors/run on grid test, 2 min - 10 min post-EtOH injection		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		06				Male			2.58		1.84		1.66		2.4				2.28		5.43																		3.18										2.25						1.84				2.5																												12/20/2002			ETGRID2.5	GT	ETGRID	EtOH	2.5 g/kg		JCC	p. 185, Table 3	MRG 120601 from publication	6683363.06
Chronic ethanol withdrawal - handling induced convulsion,  1.5 g/kg loading dose and 68.1mg/kg pyrazole; 15 hr area under curve		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		07				Male			14.5		29				34.5										23.75		21.13				22.83		16										7.5										32.5						25.33																												12/26/2002			ETHIC(VAP)	WDR	AREA	EtOH	Varied vapor conc	Exp1	JCC	p. 185, Table 4	MRG 021502 from publication	6683363.07
Chronic ethanol withdrawal - handling induced convulsion,  1.5 g/kg loading dose and 68.1mg/kg pyrazole; 15 hr area under curve		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		08				Male							28.3		29.83				11.83						41.3						25.88		11.75														15		28.17				35.3				5																														12/20/2002			ETHIC(VAP)	WDR	AREA	EtOH	Varied vapor conc	Exp2	JCC	p. 185, Table 4	MRG 021502 from publication	6683363.08
Chronic ethanol withdrawal - handling induced convulsion,  1.5 g/kg loading dose and 68.1mg/kg pyrazole; 15 hr area under curve		Male mice of parent inbred strains C57BL/6J and DBA/2J, and mice from several of the BXD/Ty Recombinant Inbred (RI) strains derived from the cross of the parent inbred strains were tested for responsiveness to ethanol. Separate groups of mice from these strains were characterized for sensitivity to ethanol's effects to increase activity in an open field and to induce ambulatory ataxia in the grid test. The strain distribution pattern of the RI strains indicated polygenic control of both responses to ethanol. Other mice from this battery were tested for acceptance of an ethanol solution, a measure related to preference drinking. This trait may be substantially influenced by a single gene. Mice were then rendered physically dependent on ethanol through inhalation of ethanol vapor for three days. Severity of handling-induced convulsions was used to index the severity of the ethanol withdrawal syndrome. The distribution of the RI strains indicated possible influence of a major gene on ethanol withdrawal severity.	Crabbe JC, Kosobud A, Young ER, Janowsky JS.	Polygenic and single-gene determination of responses to ethanol in BXD/Ty recombinant inbred mouse strains	Neurobehav Toxicol Teratol	5(2)	181-187	Mar-Apr	1983 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6683363&dopt=Abstract	6683363		09				Male			11.83		28		19.43						13.64																		8												22.75				7.5		9.83		4		23.67																												12/20/2002			ETHIC(VAP)	WDR	AREA	EtOH	Varied vapor conc	Exp3	JCC	p. 185, Table 4	MRG 021502 from publication	6683363.09
Ethanol hypothermic sensitivity 2 g/kg [degrees C]	[1)  Initial report given in Crabbe, Belknap, Mitchell, Crawshaw, 1994 JPET 269:184-192.                                2)  QTL analyses performed as described in Crabbe, Phillips, Gallaher, Crawshaw, Mitchell, 1996 JPET 277: 624-632              3)  For the '96 paper, data for additional strains were added and some additional mice.  Complete data set for the '96 paper is presented here in this database]	Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.	Crabbe JC, Phillips TJ, Gallaher EJ, Crawshaw LI, Mitchell SR.	Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.	J Pharmacol Exp Ther	277(2)	184-192	May	1996 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627539&dopt=Abstract	8627539 		92				Female		degree C	-2		-1.628		-1.153		-1.344		-2.374		-2.255		-1.231		-2.642		-0.594		-1.27		-1.296		-1.617		-0.875		-0.853		-1.439		-1.038				-1.394		-1.631				-1.328		-1.861		-0.877		-1.096		-1.908		-0.602				-1.492																								12/26/2002			ETTEMP2	HT2	AVED1E2	EtOH	2 g/kg	RI-50	JCC		JRS 2/11/00 from data file	8627539.92
Ethanol hypothermic sensitivity 3 g/kg [degrees C]	[1)  Initial report given in Crabbe, Belknap, Mitchell, Crawshaw, 1994 JPET 269:184-192.                                2)  QTL analyses performed as described in Crabbe, Phillips, Gallaher, Crawshaw, Mitchell, 1996 JPET 277: 624-632              3)  For the '96 paper, data for additional strains were added and some additional mice.  Complete data set for the '96 paper is presented here in this database]	Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.	Crabbe JC, Phillips TJ, Gallaher EJ, Crawshaw LI, Mitchell SR.	Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.	J Pharmacol Exp Ther	277(2)	624-632    	May	1996 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627539&dopt=Abstract	8627539 		91				Female		degree C	-3.1		-1.601		-2.083		-2.467		-3.174		-2.904		-1.797		-3.331		-1.008		-2.921		-2.583		-1.733		-2.528		-1.909		-2.225		-2.654				-1.793		-3.167				-1.856		-2.386		-3.146		-2.192		-2.449		-1.595				-2.363																								12/26/2002			ETTEMP3	HT3	AVED1E3	EtOH	3 g/kg	RI-50	JCC		JRS 2/11/00 from data file	8627539.91
Ethanol hypothermic sensitivity 4 g/kg [degrees C]	[1)  Initial report given in Crabbe, Belknap, Mitchell, Crawshaw, 1994 JPET 269:184-192.                                2)  QTL analyses performed as described in Crabbe, Phillips, Gallaher, Crawshaw, Mitchell, 1996 JPET 277: 624-632              3)  For the '96 paper, data for additional strains were added and some additional mice.  Complete data set for the '96 paper is presented here in this database]	Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.	Crabbe JC, Phillips TJ, Gallaher EJ, Crawshaw LI, Mitchell SR.	Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.	J Pharmacol Exp Ther	277(2)	624-632    	May	1996 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627539&dopt=Abstract	8627539 		90				Female		degree C	-3.96		-2.934		-2.233		-2.528		-3.651		-3.479		-2.109		-3.467		-1.514		-2.979		-3.73		-3.9		-3.323		-1.826		-2.71		-2.549				-2.742		-2.769				-2.403		-2.067		-4.285		-2.312		-2.922		-2.101				-3.086																								12/26/2002			ETTEMP4	HT4	AVED1E4	EtOH	4 g/kg	RI-50	JCC		JRS 2/11/00 from data file	8627539.9
Hypothermia tolerance (positive scores) or sensitization(negative scores) 2 g/kg ethanol, day 3 - day 1 [degrees C]	[1)  Initial report given in Crabbe, Belknap, Mitchell, Crawshaw, 1994 JPET 269:184-192.   2)  QTL analyses performed as described in Crabbe, Phillips, Gallaher, Crawshaw, Mitchell, 1996 JPET 277: 624-632              3)  For the '96 paper, data for additional strains were added and some additional mice.  Complete data set for the '96 paper is presented here in this database]	Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.	Crabbe JC, Phillips TJ, Gallaher EJ, Crawshaw LI, Mitchell SR.	Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.	J Pharmacol Exp Ther	277(2)	624-632    	May	1996 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627539&dopt=Abstract	8627539 		89				Female		degree C	-0.495		-0.564		-0.014		-0.225		-0.035		-0.692		-0.103		-0.408		-0.008		-2.17		-0.252		-0.597		-0.019		0.053		0.189		-0.153				-0.066		0.503				0.161		-0.295		0.108		0.424		-0.752		-0.019				-0.444																								12/26/2002			ETTEMPTOL2	TOL2	DDAV13E2	EtOH	2 g/kg	RI-50	JCC		JRS 2/11/00 from data file	8627539.89
Hypothermia tolerance (positive scores) or sensitization(negative scores) 3 g/kg ethanol, day 3 - day 1 [degrees C]	[1)  Initial report given in Crabbe, Belknap, Mitchell, Crawshaw, 1994 JPET 269:184-192.                                2)  QTL analyses performed as described in Crabbe, Phillips, Gallaher, Crawshaw, Mitchell, 1996 JPET 277: 624-632              3)  For the '96 paper, data for additional strains were added and some additional mice.  Complete data set for the '96 paper is presented here in this database]	Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.	Crabbe JC, Phillips TJ, Gallaher EJ, Crawshaw LI, Mitchell SR.	Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.	J Pharmacol Exp Ther	277(2)	624-632    	May	1996 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627539&dopt=Abstract	8627539 		88				Female		degree C	-0.907		0.058		-0.316		-0.569		0.023		-0.439		-0.181		-0.687		0.003		-0.697		-0.164		0.1		-0.991		-0.338		-0.366		-0.759				0.727		-0.178				1.122		-0.505		-0.492		-5.13		-0.179		-0.464				-0.229																								12/26/2002			ETTEMPTOL3	TOL3	DDAV13E3	EtOH	3 g/kg	RI-50	JCC		JRS 2/11/00 from data file	8627539.88
Hypothermia tolerance (positive scores) or sensitization(negative scores) 4 g/kg ethanol, day 3 - day 1 [degrees C]	[1)  Initial report given in Crabbe, Belknap, Mitchell, Crawshaw, 1994 JPET 269:184-192.                                2)  QTL analyses performed as described in Crabbe, Phillips, Gallaher, Crawshaw, Mitchell, 1996 JPET 277: 624-632              3)  For the '96 paper, data for additional strains were added and some additional mice.  Complete data set for the '96 paper is presented here in this database]	Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.	Crabbe JC, Phillips TJ, Gallaher EJ, Crawshaw LI, Mitchell SR.	Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.	J Pharmacol Exp Ther	277(2)	624-632    	May	1996 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627539&dopt=Abstract	8627539 		87				Female		degree C	-0.78		-0.922		0.097		-0.354		-0.679		-0.863		0.136		-0.025		-0.356		-0.363		-0.667		-1.278		-1.139		0.108		-0.465		-0.559				-0.5		-0.343				0.444		-0.6		0.722		-0.573		-0.381		-1.031				-0.972																								12/26/2002			ETTEMPTOL4	TOL4	DDAV13E4	EtOH	4 g/kg	RI-50	JCC		JRS 2/11/00 from data file	8627539.87
Baseline Temp (C) for Day 1 before Quinpirole injection 		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet  	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		01	10-14 wks	70	98	Female			38.711		38.687				38.851		38.724		38.69		39.37		38.721		39.227		38.958		38.581		38.645		38.565		38.369		38.192		38.247				39.009		39.074		38.79		38.453		39.183		38.67		38.7		39.449		38.46		38.168		39.068																								12/20/2002			NULTEMP	BASET	BASECD1	Quinpirole	1mg/kg	RI-69	JCC		JD 121901  from data file	11054779.01
Hypothermia measured 60 min after quinpirole administration on day 1; change from baseline temperature [degrees C] 		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		02	10-14 wks	70	98	Female		degrees C	-1.622	0.200	-5.043	0.243			-3.847	0.296	-1.144	0.210	-3.634	0.252	-4.746	0.390	-4.374	0.343	-1.224	0.157	-2.074	0.152	-0.874	0.233	-2.673	0.204	-1.127	0.091	-2.798	0.273	-1.573	0.314	-6.465	0.324			-3.295	0.272	-1.781	0.181	-3.488	0.309	-2.557	0.168	-2.4	0.271	-3.615	0.305	-6.767	0.590	-2.089	0.195	-3.831	0.315	-1.115	0.117	-3.967	0.258																							7/1/2003	MK Sullivan		QPTEMP1	HT60	DEL60D1	Quinpirole	1mg/kg	RI-69	JCC	p. 700, Fig 2a	JD 121901  from data file	11054779.02
Tolerance to quinpirole induced hypothermia on day 2 as compared to day 1 [degrees C]		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		03	10-14 wks	70	98	Female		degrees C	-0.242		-0.735				-0.918		-0.18		-1.153		-1.407		-1.184		-0.34		-0.056		-0.202		-0.386		0.03		-0.768		-0.636		-2.019				-0.754		-0.542		-1.215		-0.457		-0.692		-0.688		-2.167		-0.461		-1.024		-0.226		-1.718																											QPTEMPTOL1(D2)	HT TOL2	TOL60D12	Quinpirole	1mg/kg	RI-69	JCC		JD 121901  from data file	11054779.03
Tolerance to quinpirole induced hypothermia on day 3 as compared to day 1 [degrees (C)]		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		04	10-14 wks	70	98	Female		degrees C	-0.758	0.158	-1.652	0.262			-1.472	0.214	-0.262	0.177	-2.213	0.205	-2.151	0.328	-1.412	0.295	-0.636	0.214	-0.234	0.159	-0.139	0.162	-0.978	0.199	-0.296	0.150	-1.374	0.270	-1.015	0.214	-3.181	0.402			-1.102	0.266	-0.936	0.193	-1.321	0.208	-1.038	0.167	-0.575	0.243	-0.528	0.281	-2.867	0.476	-1.222	0.178	-0.569	0.210	-0.390	0.121	-2.197	0.223																							7/2/2003	MK Sullivan		QPTEMPTOL1(D3)	HT TOL3	TOL60D13	Quinpirole	1mg/kg	RI-69	JCC	p. 700, Fig 2b	JD 121901  from data file	11054779.04
Activity after saline administration (baseline); distance traveled [cm]		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet  	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		05	10-14 wks	70	98	Female	10-44	cm	4856.45	294.2	3130	174.3			3465.56	133.6	2872.5	20.3	4197.17	309.1	3103.19	197.1	3973.81	124.9	1348.96	157.7	4790.5	236.5	2741.05	256.0	4112.67	231.5	4431	334.0	2289.59	150.2	4913.86	286.7	3254.37	190.9			3430.68	223.7	2475.78	136.9	2849.41	155.6	1952.25	83.8	4462.47	345.2	2008.57	158.5	2237.4	128.6	6160.66	266.4	3338.65	144.8	3182.64	161.4	4400.74	207.5																							7/1/2003	MK Sullivan		SALACT	ACT BASAL	STHDIST	Saline		RI-69	JCC	p. 699, Fig 1a	JD 121901  from data file	11054779.05
Activity decrease after administration of 0.01 mg/kg  quinpirole; difference from basal activity, distance traveled [cm] 		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		06	10-14 wks	70	98	Female	10-44	cm	-2878.27	407.2	-843.33	202.3			-1327.56	190.2	-1165.64	136.6	-2840.87	341.5	-1098.64	262.6	-1016.06	152.1	-735.08	241.8	-3267.53	356.7	-1597.27	427.6	-956.22	319.3	-1714.36	586.3	-999.5	213.4	-2063.09	260.1	-1038.57	178.4			-1214.11	260.8	-1095.88	164.9	-902.82	251.3	-848.6	108.2	-1845.5	309.3	-459.14	196.4	-786.2q	228.9	-2773.6	301.0	-914.67	238.1	-1319.57	193.0	-1696.27	277.8																							7/1/2003	MK Sullivan		QPACT.01(delta)	ACT DECR01	DELHD01	Quinpirole	.01 mg/kg	RI-69	JCC		JD 121901  from data file	11054779.06
Activity decrease after administration of 0.03 mg/kg  quinpirole; difference from basal activity, distance traveled [cm]		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		07	10-14 wks	70	98	Female			-2963.64		-1541.71				-1777.94		-1658.43		-2678.6		-1934.9		-1839.38		-808.92		-3388.47		-1582		-2256.11		-2761.92		-1368.38		-2667.27		-2029.77				-1945.8		-1501.44		-1162.07		-1158.05		-1969.09		-717.06		-1669.6		-3768.1		-1573.64		-1691.86		-2403.35																								12/20/2002			QPACT.03(delta)	ACT DECR03	DELHD03	Quinpirole	.03 mg/kg	RI-69	JCC	p. 699, Fig 1b	JD 121901  from data file	11054779.07
Rearing after saline administration [number of beam interruptions]	[Unpublished means from same series of studies as reported in:     Buck, Lischka, Dorow, Crabbe, 2000  AmerJMedGenet (NeuropsychiGenet) 96:696-705]	Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		86	10-14 wks	70	98	Female		number of beam interruptions	277.448		356.462				173.882		167.357		263.933		330.952		357.313		114.48		273		195.545		214.556		220.783		184.235		249.455		272.741				296.737		99.813		214.813		84.85		299.158		118.467		136.8		282		335.217		210.048		380.095																								12/19/2002			SALREAR	REAR BASAL	STVACT	Saline		RI-69	JCC		JD 121901  from file	11054779.86
Rearing decrease after 0.01 mg/kg quinpirole; difference from basal rearing, [number of beam interruptions]		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet  	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		85	10-14 wks	70	98	Female			-124.267		-77.33				-27.375		-57.286		-164.4		-101.636		-86.125		-54.615		-150.53		-105.091		-23.333		-52.182		-64		-20.364		-88.571				-62.667		-31.875		-72.706		-33.1		-126.25		9.571		-32		-102.1		-49.5		-55.333		-153.273																								12/19/2002			QPREAR.01(delta)	REAR DECR01	DELVAC01	Quinpirole	.01 mg/kg	RI-69	JCC		JD 121901  from file	11054779.85
Rearing decrease after 0.03 mg/kg quinpirole; difference from basal rearing, [number of beam interruptions]		Acute sensitivity and tolerance to quinpirole (a dopamine mimetic with selectivity for D(2)/D(3) dopamine receptors) were evaluated in the C57BL/6J and DBA/2J inbred strains of mice, 24 of their BXD recombinant inbred strains, and 233 F(2) mice. Baseline locomotor activity, locomotor activity following 0.03 mg/kg quinpirole (and 0. 01 mg/kg in BXD mice), body temperature following 1 mg/kg quinpirole, and hypothermic tolerance following 2 or 3 days of quinpirole administration were evaluated. Quantitative trait locus (QTL) analysis was employed to identify genetic determinants of baseline locomotor activity and five behavioral responses to quinpirole. We examined correlated allelic variation in genetic markers of known chromosomal location with variation in each of these phenotypes. We definitively mapped a QTL on Chromosome (Chr) 9 linked to the D(2) dopamine receptor gene, Drd2, for hypothermic sensitivity to quinpirole, and identify a suggestive QTL in the same chromosomal region for tolerance to quinpirole after repeated treatments. Suggestive QTLs were also identified on Chr 19 for sensitivity and tolerance to quinpirole-induced hypothermia and for baseline locomotor activity; on Chr 15 for locomotor sensitivity to quinpirole; and on Chr 13 and 5 for baseline locomotor activity. Our results indicate that genetic differences in quinpirole sensitivity and tolerance are associated with QTLs near Drd2, and that baseline locomotor activity is associated with a suggestive QTL in proximity to the dopamine transporter gene Dat1. These data suggest that the genes influencing locomotor activity, dopamine mimetic sensitivity, and tolerance do not overlap completely.	Buck K, Lischka T, Dorow J, Crabbe J.	Mapping quantitative trait loci that regulate sensitivity and tolerance to quinpirole, a dopamine mimetic selective for D(2)/D(3) receptors	Amer J Med Genet 	96(5)	696-705	Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054779&dopt=Abstract	11054779		84	10-14 wks	70	98	Female			-184.5		-180.286						-66.56		-79.571		-137.2		-168.2		-120.875		-74.833		-201.2		-104.545		-120.333		-120.167		-115.38		-83.273				-148.308		-179.4		-77.625		-78.267		-29.1		-162.909		-20.25		-89.2		-123.714		-157.27		-107.714																						-216.857		12/19/2002			QPREAR.03(delta)	REAR DECR03	DELVAC03	Quinpirole	.03 mg/kg	RI-69	JCC		JD 121901  from file	11054779.84
BEC (blood ethanol concentration) from the retro-orbital sinus at recovery of righting reflex [mg/ml]		BACKGROUND: Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. METHODS: We conducted a QTL analysis of ethanol-induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen. RESULTS: Genome-wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p < or = 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 13, and X, and several map near potential candidate genes. CONCLUSIONS: These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.	Browman KE, Crabbe JC.	Quantitative trait loci affecting ethanol sensitivity in BXD recombinant inbred mice	Alcohol Clin Exp Res	24(1)	17-23	Jan	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10656187&dopt=Abstract	10656187		01	8-18 wks	56	126	Female	4-18	mg/ml	3.915	0.231	3.58	0.098	3.788	0.070	3.46	0.087	3.966	0.104	3.453	0.079	3.971	0.101			3.894	0.100	3.406	0.114	3.837	0.048	3.846	0.078	3.899	0.178	3.446	0.078	3.547	0.124	3.266	0.128			3.581	0.125	3.406	0.099	4.084	0.136	3.813	0.106	3.651	0.073	4.121	0.162	4.002	0.084	3.757	0.109	4.129	0.155	3.634	0.073	3.843	0.140																							7/16/2003	MK Sullivan		ETLORRBEC4.1	LRRBEC	BEC            LORR	EtOH	4.1 g/kg     20% V/V 	RI-80	JCC	p.19, Fig 1A	JRS 2/11/00 and JD with JCC 020702	10656187.01
Duration of post-ethanol loss of righting reflex [minutes]		BACKGROUND: Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. METHODS: We conducted a QTL analysis of ethanol-induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen. RESULTS: Genome-wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p < or = 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 13, and X, and several map near potential candidate genes. CONCLUSIONS: These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.	Browman KE, Crabbe JC. 	Quantitative trait loci affecting ethanol sensitivity in BXD recombinant inbred mice	Alcohol Clin Exp Res	24(1)	17-23	Jan	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10656187&dopt=Abstract	10656187		02	8-18 wks	56	126	Female	4-18	minutes	88.222	9.55	87.254	7.01	130.45	15.74	172.442	10.07	114.3	21.78	131.204	18.04	93.668	10.82			82.472	8.71	176.828	10.60	148.655	22.79	94.72	7.75	122.329	7.75	124.98	24.83	182.56	21.34	194.169	28.89			132.467	16.44	155.08	27.73	111.9	15.81	138.067	8.02	113.967	6.26	161.538	35.27	118.362	13.22	122.59	10.07	56.071	5.07	124.086	8.59	178.463	21.01																							7/16/2003	MK Sullivan		ETLORR4.1	LRRDUR	DURATION   LORR	EtOH	4.1 g/kg     20% V/V 	RI-80	JCC	p.19, Fig 1B	JRS 2/11/00 and JD with JCC 020702	10656187.02
Ethanol induced ataxia - Screen test sensitivity, latency to fall, saline response minus 2.5 g/kg Ethanol response [seconds] 	[NOTE: dose was reported incorrectly in the cited publication]	BACKGROUND: Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. METHODS: We conducted a QTL analysis of ethanol-induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen. RESULTS: Genome-wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p < or = 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 13, and X, and several map near potential candidate genes. CONCLUSIONS: These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.	Browman KE, Crabbe JC. 	Quantitative trait loci affecting ethanol sensitivity in BXD recombinant inbred mice	Alcohol Clin Exp Res	24(1)	17-23	Jan	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10656187&dopt=Abstract	10656187		03	7-20	49	140	Female	4-18	seconds	45.155	3.30	16.107	6.19	43.169	4.02	43.434	0.04	27.264	11.30	33.383	6.15	42.943	4.77	35.512	8.25	16.804	7.27	41.471	1.99	36.536	6.04	36.324	5.05	36.524	6.26	46.496	4.28	40.204	4.76	30.813	7.18			35.676	5.87	27.141	7.75	25.203	13.78	21.797	6.97	32.526	6.79	28.99	8.60	39.616	7.68	49.821	1.21	24.452	8.69	46.511	5.34	40.265	3.61																							7/16/2003	MK Sullivan		ETSCR2(delta)	SCREEN	DELLAT        SCREEN	EtOH	2.5g/kg	RI-80	JCC	p.19, Fig 1C	JRS 2/11/00 and JD with JCC 020702	10656187.03
Area under the 25-hr curve for withdrawal following 72 hr exposure to EtOH vapor. Pyrazole injections were given daily to inhibit EtOH metabolism. Handling-induced convulsions (HIC) were scored hourly for 10 hr and again at hrs 24 and 25 [seizure severity]		Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI) strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for 72 hr. Mice were selected such that each strain averaged 1.34 to 1.59 mg of EtOH/ml of blood on withdrawal. Control groups and EtOH-exposed groups were tested hourly for handling-induced convulsions (HIC) for 10 hr and at hr 24 and 25. Strain withdrawal severity was indexed as the area under the 25-hr HIC curve for the EtOH group minus that strain's equivalent value for the control group. Genome-wide quantitative trait locus (QTL) analyses correlating strain means with allelic status at > 1500 markers identified 10 chromosomal regions at P < .01. These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2 QTLs), 10, 12, 13, 15 and 18. Multiple regression analysis using the four most influential QTLs revealed that these loci controlled 86% of the genetic variance. A QTL mapped to distal chromosome 1 (P < .001) is in the same region as one previously definitively mapped for acute alcohol withdrawal, as well as one mapped for acute pentobarbital withdrawal. Several of the QTLs map near potential candidate genes. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.	Crabbe JC 	Provisional mapping of quantitative trait loci for chronic ethanol withdrawal severity in BXD recombinant inbred mice	J Pharmacol Exp Ther	286(1)	263-271	Jul	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9655868&dopt=Abstract	9655868		01				Male	3-58	seizure severity:0= no response; 4 or 5= sever tonic or clonic convulsions; 6 or 7= sever or tonic convulsions after mouse released 	42.65	1.85	77.11	3.44	58	2.64	83.25	3.94	72.21	7.25	33.65	3.99	54.75	5.60	74.69	3.84	65.24	4.50	48.41	3.04	66.86	4.23	49.03	3.63	29.78	11.77	36.19	5.78	30.38	4.05	7.19	1.70			56.1	2.44	58.57	4.73	78.33	0.63	68.42	6.98	59.71	9.10	58.86	4.31	46.93	4.65	14.77	2.84	70.25	4.78	5.5	1.75	57.88	4.60																							6/19/2003	MK Sullivan		ETHIC(VAP)	AREA25	AREA25      ETMEAN	EtOH	1.5 mg/ml blood	RI-106	JCC	p. 267, Fig 7	EQ 2/9/00 and JD 020702	9655868.01
Area under the 25-hr curve for withdrawal following 72 hr exposure to air. Pyrazole injections were given daily to inhibit EtOH metabolism. Handling-induced convulsions (HIC) were scored hourly for 10 hr and again at hrs 24 and 25 [seizure severity]		Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI) strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for 72 hr. Mice were selected such that each strain averaged 1.34 to 1.59 mg of EtOH/ml of blood on withdrawal. Control groups and EtOH-exposed groups were tested hourly for handling-induced convulsions (HIC) for 10 hr and at hr 24 and 25. Strain withdrawal severity was indexed as the area under the 25-hr HIC curve for the EtOH group minus that strain's equivalent value for the control group. Genome-wide quantitative trait locus (QTL) analyses correlating strain means with allelic status at > 1500 markers identified 10 chromosomal regions at P < .01. These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2 QTLs), 10, 12, 13, 15 and 18. Multiple regression analysis using the four most influential QTLs revealed that these loci controlled 86% of the genetic variance. A QTL mapped to distal chromosome 1 (P < .001) is in the same region as one previously definitively mapped for acute alcohol withdrawal, as well as one mapped for acute pentobarbital withdrawal. Several of the QTLs map near potential candidate genes. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.	Crabbe JC 	Provisional mapping of quantitative trait loci for chronic ethanol withdrawal severity in BXD recombinant inbred mice	J Pharmacol Exp Ther	286(1)	263-271	Jul	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9655868&dopt=Abstract	9655868		02				Male	3-24	seizure severity:0= no response; 4 or 5= sever tonic or clonic convulsions; 6 or 7= sever or tonic convulsions after mouse released 	9.9	1.90	15.54	3.69	29.19	4.24	7.72	2.84	39	4.73	1.71	0.92	38.58	5.23	24	3.99	6.06	3.78	24.33	5.93	35.38	6.68	4.28	1.55	2.21	1.40	2.67	0.71	3.5	1.94	0	0			10.85	3.74	13.57	5.42	4.83	0.64	3.19	1.71	0.67	0	8.31	2.10	5.33	1.71	0.08	0	31.22	3.99	0.22	0	0.29	0																							6/19/2003	MK Sullivan		PYRHIC68.1(VAP)	PYRAREA25	PYRAREA25  SALMEAN	Air/Pyrazole		RI-106	JCC	p. 267, Fig 7	EQ 2/9/00 and JD 020702	9655868.02
EtOH withdrawal severity corrected for differences in HIC (handling-induced convulsions) response to pyrazole. Difference between strain mean values for AREA25 and PYRAREA25 [seizure severity]		Male mice from C57BL/6J (B6), DBA/2J (D2) and their 25 recombinant inbred (RI) strains were exposed to ethanol (EtOH) vapor (3.0-9.0 mg EtOH/liter of air) for 72 hr. Mice were selected such that each strain averaged 1.34 to 1.59 mg of EtOH/ml of blood on withdrawal. Control groups and EtOH-exposed groups were tested hourly for handling-induced convulsions (HIC) for 10 hr and at hr 24 and 25. Strain withdrawal severity was indexed as the area under the 25-hr HIC curve for the EtOH group minus that strain's equivalent value for the control group. Genome-wide quantitative trait locus (QTL) analyses correlating strain means with allelic status at > 1500 markers identified 10 chromosomal regions at P < .01. These provisionally identified QTLs were on chromosomes 1 (2 QTLs), 3, 9 (2 QTLs), 10, 12, 13, 15 and 18. Multiple regression analysis using the four most influential QTLs revealed that these loci controlled 86% of the genetic variance. A QTL mapped to distal chromosome 1 (P < .001) is in the same region as one previously definitively mapped for acute alcohol withdrawal, as well as one mapped for acute pentobarbital withdrawal. Several of the QTLs map near potential candidate genes. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.	Crabbe JC 	Provisional mapping of quantitative trait loci for chronic ethanol withdrawal severity in BXD recombinant inbred mice	J Pharmacol Exp Ther	286(1)	263-271	Jul	1998 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9655868&dopt=Abstract	9655868		03				Male	3-58	seizure severity:0= no response; 4 or 5= sever tonic or clonic convulsions; 6 or 7= sever or tonic convulsions after mouse released 	32.75	1.90	61.57	3.48	29.01	2.46	75.53	3.94	33.21	3.52	31.94	4.05	16.17	5.36	50.69	3.87	59.17	4.57	24.08	3.09	31.48	4.18	44.76	3.54	27.56	11.60	33.52	5.67	26.88	4.00	7.19	1.87			45.25	2.30	45	4.67	73.5	0.79	65.24	7.11	59.05	8.97	50.56	4.30	41.6	4.03	14.69	2.94	39.03	4.64	5.28	1.56	57.58	4.48																							6/19/2003	MK Sullivan		ETHIC(VAPdelta)	DELAREA25	DELAREA25  WDR              DIFFAR	EtOH	1.5 mg/ml blood	RI-106	JCC	p. 267, Fig 8	EQ 2/9/00 and JD 020702	9655868.03
Locomotor activity.  Corn Oil, 30 minute test.		Genetic mechanisms responsible for organophosphate (OP)-induced behavioral changes remain obscure. In the present study, provisional quantitative trait loci (QTL) associated with acute sensitivity or insensitivity to hypolocomotion produced by the OP paraoxon were identified. Naive adult male and female mice of the BXD/Ty series (22 different BXD strains plus C57BL/6J and DBA/2J progenitor strains) received 0 or 0.25 mg/kg paraoxon (IP), immediately before placement in an activity chamber for a 30-min test. As expected, based on dose-response and time course studies with Swiss-Webster, C57BL/6, and DBA/2 mice, paraoxon treatment reduced locomotor activity in most, but not all BXD strains. Heritability (proportion of phenotypic variability attributed to genetic differences) was 0. 58 for the paraoxon treatment effect. Difference scores (strain mean for vehicle activity minus strain mean for paraoxon activity), and percent change in activity of paraoxon-treated mice compared to vehicle-treated mice were calculated for each BXD strain. QTL analyses using activity difference scores and percentage change in activity were conducted using a database with over 1300 unique genetic markers. Several provisional QTL found on different chromosomes were associated with the activity phenotype. Of these, several markers attained p<0.01 or greater. These were as follows: Chr 1: Ly9, p<0.006; Chr 6: D6Ncvs44, p<0.0005; Chr 9: D9Mit15, p<0. 003; Chr 11: D11Ncvs76, p<0.002; Chr 15: Tstap198, p<0.008. In addition, several markers on chromosome 3 approached p<0.01. Identified genes found near these regions include two plasma carboxylesterase alleles on chromosomes 6 and 9, a glutamate receptor subtype on chromosome 11 and a glycine receptor subunit on chromosome 11, raising the possibility that these genes could be the basis for these provisional QTLs.	Risinger FO, Quick E, Belknap JK	Quantitative trait loci for acute behavioral sensitivity to paraoxon	Neurotoxicol Teratol	22(5)	667-674	Sep-Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11106859&dopt=Abstract	11106859		02	7 wks	49		Male			46.7		46.2		57.3		33.2		27		52.5		36.1				30.9		39.3		31.6		49.1		31.2		31.7		39		44.4				40.8						25.3		40.9		33.3		24.1		55.9		31.3		36.8		41.6																								12/26/2002			OILACT		OILACT	Corn Oil	10ml/kg		FOR	p. 671, Fig 1	MRG with FOR from files and publication 021402	11106859.02
Locomotor activity.  Paraoxon, 30 minute test.		Genetic mechanisms responsible for  organophosphate (OP)-induced behavioral changes remain obscure. In the present study, provisional quantitative trait loci (QTL) associated with acute sensitivity or insensitivity to hypolocomotion produced by the OP paraoxon were identified. Naive adult male and female mice of the BXD/Ty series (22 different BXD strains plus C57BL/6J and DBA/2J progenitor strains) received 0 or 0.25 mg/kg paraoxon (IP), immediately before placement in an activity chamber for a 30-min test. As expected, based on dose-response and time course studies with Swiss-Webster, C57BL/6, and DBA/2 mice, paraoxon treatment reduced locomotor activity in most, but not all BXD strains. Heritability (proportion of phenotypic variability attributed to genetic differences) was 0. 58 for the paraoxon treatment effect. Difference scores (strain mean for vehicle activity minus strain mean for paraoxon activity), and percent change in activity of paraoxon-treated mice compared to vehicle-treated mice were calculated for each BXD strain. QTL analyses using activity difference scores and percentage change in activity were conducted using a database with over 1300 unique genetic markers. Several provisional QTL found on different chromosomes were associated with the activity phenotype. Of these, several markers attained p<0.01 or greater. These were as follows: Chr 1: Ly9, p<0.006; Chr 6: D6Ncvs44, p<0.0005; Chr 9: D9Mit15, p<0. 003; Chr 11: D11Ncvs76, p<0.002; Chr 15: Tstap198, p<0.008. In addition, several markers on chromosome 3 approached p<0.01. Identified genes found near these regions include two plasma carboxylesterase alleles on chromosomes 6 and 9, a glutamate receptor subtype on chromosome 11 and a glycine receptor subunit on chromosome 11, raising the possibility that these genes could be the basis for these provisional QTLs.	Risinger FO, Quick E, Belknap JK	Quantitative trait loci for acute behavioral sensitivity to paraoxon	Neurotoxicol Teratol	22(5)	667-674	Sep-Oct	2000 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11106859&dopt=Abstract	11106859		01	7 wks	49		Male			29		14.2		26.3		42.6		14.4		39		24.3				14.9		20.4		11.4		33.8		16.7		15.1		31.3		22.7				17.1						9.9		24.7		26.6		12.5		36.6		25		15		12.2																								12/26/2002			PARAOX		PARAOX	Paraoxon	0.25mg/kg		FOR	p. 671, Fig 1	MRG with FOR from files and publication 021402	11106859.01
54 degree C hot plate latencies baseline (before 3 min forced swim in 15 degree C water) MF [seconds]		It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.	Mogil JS, Richards SP, O'Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK.	Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice	J Neurosci	17(20)	7995-8002	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9315917&dopt=Abstract	9315917	97461641	01	8-12 wks	56	96	MF	9-26	seconds	19.1	1.2	24.3	1.6	22.6	 0.9	19.4	1.6	18.3	1.7	19.8	1.8	28.6	2.1	19.8	2.1	18.1	1.7	24.5	1.7	23.9	2.3	24.6	2.2	18.3	1.6	15.1	1.5	25.9	1.7	16.1	1.5			20.9	1.5	24.6	3.2	15.9	2.1			24.2	2.0	20.4	1.8	18.3	1.3	17.9	1.3	18.9	1.1	13	1.1	13.6	1.2																							7/3/2003	MK Sullivan											9315917.01
54 degree C hot plate latencies baseline (before 3 min forced swim in 15 degree C water), Female [seconds]		It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.	Mogil JS, Richards SP, O'Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK.	Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice	J Neurosci	17(20)	7995-8002	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9315917&dopt=Abstract	9315917	97461641	02	8-12 wks	56	96	Female	3-10	seconds	20.5	1.4	22.2	2.4	21.4	0.6	20	2.4	17.1	2.3	19.9	2.9	27.3	2.8	16.3	2.2	14.9	1.7	26	2.8	21.3	2.2	18.7	1.2	16.5	2.7	15.9	0.6	23.6	2.7	15.2	2.3			20.7	2.7	17.3	5.5	13.5	2.1			19.5	2.1	21.3	1.9	17.4	1.7	16.9	1.9	18	1.6	12.6	1.3	12.4	1.3																							7/3/2003	MK Sullivan											9315917.02
54 degree C hot plate latencies baseline (before 3 min forced swim in 15 degree C water), Male [seconds]		It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.	Mogil JS, Richards SP, O'Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK.	Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice	J Neurosci	17(20)	7995-8002	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9315917&dopt=Abstract	9315917	97461641	03	8-12 wks	56	96	Male	4-18	seconds	17.5	1.9	26.1	2.0	23.7	1.7	18.9	2.1	19.8	2.5	19.7	2.2	30.5	3.2	26.6	1.9	22.1	2.6	23	2.1	26.6	4.0	29.7	2.8	20.3	1.6	14.1	3.2	27.4	2.1	17	1.9			21	1.4	28.2	3.2	18.2	3.5			27.9	2.8	19.5	3.3	19.2	1.9	18.8	1.8	19.9	1.6	13.3	1.7	14.7	2.0																							7/3/2003	MK Sullivan											9315917.03
54 degree C hot plate latencies Post-Swim MF [seconds]		It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.	Mogil JS, Richards SP, O'Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK.	Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice	J Neurosci	17(20)	7995-8002	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9315917&dopt=Abstract	9315917	97461641	04	8-12 wks	56	96	MF	9-26	seconds	46.5	4.3	42.5	3.9	58.2	1.2	32.5	3.8	48.2	4..8	50.6	3.0	52.1	3.5	55.5	3.1	52.5	3.6	55.1	2.1	60	0	35.8	4.6	43.9	3.6	49.6	3.6	51.5	3.0	33.1	3.1			56.4	3.2	44.2	6.5	37	4.0			54.9	2.6	54.5	2.3	50.7	3.3	33.4	4.0	34.2	5.0	24.6	4.2	41.4	3.3																							7/3/2003	MK Sullivan											9315917.04
54 degree C hot plate latencies Post-Swim Female [seconds]		It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.	Mogil JS, Richards SP, O'Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK.	Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice	J Neurosci	17(20)	7995-8002	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9315917&dopt=Abstract	9315917	97461641	05	8-12 wks	56	96	Female	3-10	seconds	46.7	5.0	39.1	4.5	58.1	1.9	29.6	3.2	51.6	5.9	51.3	4.4	54.2	3.3	53.2	4.4	54.5	3.8	55.4	3.3	60	0	30	7.5	39.4	5.7	50.2	5.1	47.7	6.2	34.0	4.4			60	0	31.7	14.2	31.5	5.5			57.1	2.9	60	0	47.1	4.4	33.4	5.2	28	6.1	14.7	2.4	44.4	4.6																							7/3/2003	MK Sullivan											9315917.05
54 degree C hot plate latencies Post-Swim Male [seconds]		It is increasingly appreciated that the sexes differ in their perception of noxious stimuli and in their responsivity to exogenous and endogenous analgesic manipulations. We previously reported the existence of qualitative sex differences in the neurochemical mediation of nonopioid (i.e., naloxone-insensitive) stress-induced analgesia (SIA) produced by forced swims and suggested that female mice possess a sex-specific SIA mechanism. This female-specific system is now known to be estrogen-dependent, to be ontogenetically organized, and to vary with reproductive status; however, its neurochemical identity remains obscure. In an attempt to identify candidate genes underlying SIA in both sexes, we performed a two-phase quantitative trait locus (QTL) mapping experiment using the BXD/Ty recombinant inbred (RI) set derived from DBA/2J (D2) and C57BL/6J (B6) inbred mouse strains and (B6xD2)F2 hybrid mice derived from these same progenitors. All mice were subjected to 3 min forced swims in 15 degrees C water; nociceptive sensitivity on the 54 degrees C hot-plate assay was assessed immediately before and 2 min after cessation of the swim. We report the localization of a QTL statistically associated with SIA magnitude [p = 0.00000012; logarithm of the odds (LOD) = 6.1] in female mice only. This female-specific QTL, which we name Fsia1, is located on chromosome 8 at 52-84 cM from the centromere and accounts for 17-26% of the overall trait variance in this sex. The present data provide further evidence of the existence of a female-specific SIA mechanism and highlight the important role of both genetic background and gender in the inhibition of pain.	Mogil JS, Richards SP, O'Toole LA, Helms ML, Mitchell SR, Kest B, Belknap JK.	Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice	J Neurosci	17(20)	7995-8002	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9315917&dopt=Abstract	9315917	97461641	06	8-12 wks	56	84	Male	4-18	seconds	46.2	7.7	45.6	6.3	58.3	1.7	35.1	6.6	44.2	8.0	49.9	4.4	49.1	7.2	60.0	0.0	49.8	7.0	54.7	2.7	60.0	0.0	40.9	5.5	48.8	3.8	48.8	5.5	53.9	3.1	32.1	4.5			52.7	6.3	50.5	6.0	42.6	5.5			53.2	4.1	48.9	3.8	54.3	4.8	33.5	6.2	40.1	7.7	32.3	6.2	38.6	4.8																							7/3/2003	MK Sullivan											9315917.06
Acoustic startle response to a 110 dB SPL, 10 kHz tone without prepulse stimulus[g]		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R 	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	06	100 days	100		MF	9-15	g	23.6		14.1		23.5				10.7		30.7		10.3		5.6		17.2		14.2		16.3		18.3		14.4		26.2		6.7		18.9				7.9		7.9		2.1		26.4		14.2		57.3		10.6		24.7		15.1		20.7		18.1																								6/6/2002	Ryan McNeive	Ryan McNeive										10371755.06
High frequency hearing loss and cochlear pathology; Acoustic startle response to 10 kHz white-noise bursts at 100 dB [g]		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	02	100 days	100		MF	9-15	g	14.7		10.2		6.7				5.2		19.4		6.2		2.1		6		11.5		6.4		4.9		11		13.9		2.5		9.4				1.8		3.4		1.3		10.8		3.8		42.2		10		4		11.7		7.6		4.7																								12/26/2002	Ryan McNeive	Ryan McNeive										10371755.02
High frequency hearing loss and cochlear pathology; Acoustic startle response to 20 kHz white-noise bursts at 100 dB [g] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	04	100 days	100		MF	9-15	g	9.1		6.3		6.4				3.4		13		2.1		2.2		6.4		10.6		5.2		8.5		8.6		14.7		2		4.7				5.5		4.1		1.2		11		3.6		31.6		7.4		3.6		17.4		7.8		2.1																								12/26/2002	Ryan McNeive	Ryan McNeive										10371755.04
High frequency hearing loss and cochlear pathology; Acoustic startle response to  5 kHz white-noise bursts at 100 dB SPL [g] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	01	100 days	100		MF	9-15	g	0.3		1.1		0.4				0.4		5.3		2.8		0.1		1.5		2.7		0.8		-0.1		1.8		4.9		0.1		6.4				-0.5		0.8		0.8		1.7		-0.4		8.8		-1		0.6		0.1		0.5		1.7																								12/26/2002	Ryan McNeive	Ryan McNeive										10371755.01
High frequency hearing loss and cochlear pathology; Acoustic startle response to 15 kHz white-noise bursts at 100 dB SPL [g] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	03	100 days	100		MF	9-15	g	21.4		7.3		9.9				5.1		14.8		2		2.4		8.8		10		5.2		10.4		7.6		18.1		4.6		7.8				3.6		5		1		15.4		5.2		39.5		7.4		3.4		24.9		9.9		3.6																								12/26/2002	Ryan McNeive	Ryan McNeive										10371755.03
High frequency hearing loss and cochlear pathology; Acoustic startle response to 25 kHz white-noise bursts at 100 dB SPL [g] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	05	100 days	100		MF	9-15	g	2.9		1.8		2.4				2		3.4		-0.4		1.4		2.1		4.1		2.2		1		4.6		10.4		0.9		1.4				-0.2		0.6		-0.5		-0.2		1.2		16		0.2		1.4		4.4		2.5		-0.8																								12/26/2002	Ryan McNeive	Ryan McNeive										10371755.05
High frequency hearing loss and cochlear pathology; Acoustic startle response to white-noise bursts at 110 dB SPL [g] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	07	100 days	100		MF	9-15	g	24.3		7.4		14.5				11.7		23.5		12.1		7.5		15.9				10.9		12.4		13.2		21.1		2.6		17.1				2.1		5.5		3.6		20.2		11.3		47.1		12.1		10.1		21.3		16.4		20.9																								6/6/2002	Ryan McNeive	Ryan McNeive										10371755.07
Alcohol acceptance total consumption over 24 hr female [g/kg]		Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.	Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE	Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains.	Alcohol Clin Exp Res	18(6)	1416-1422	Dec	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695038&dopt=Abstract	7695038	95209059	01	71-91 days	71	91	Female	8-20	g/kg	20.21		9.18		15.99		15.76		19.37		17.07		12.32		11.03		18.78		116.25		14.88		18.6				21.47		13.51						21.97		15.52				10.85		12.45		10.88		9.63		15.71				18.19		10.39																								7/11/2003	MK Sullivan		ACCB alcohol acceptance									7695038.01
Alcohol acceptance total consumption over 24 hr male [g/kg]		Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.	Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE	Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains.	Alcohol Clin Exp Res	18(6)	1416-1422	Dec	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695038&dopt=Abstract	7695038	95209059	02	71-91 days	71	91	Male	7-21	g/kg	16.84		10.22		16.1		14.96		15.26		13.48		11.46		7.73		16.78		14.43		10.03		10.35				14.77		7.08						16.47		14.66				5.12		11.71		12.06		11.73		15.57				15.58		12																								7/11/2003	MK Sullivan		ACCB alcohol acceptance									7695038.02
Alcohol acceptance - consumption of 10% ethanol in 24 hours after 24 hours of water deprivation [g/kg]		Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (RI) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e), for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7), and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.	Rodriguez LA,Ę Plomin R,ĘBlizard DA,ĘJones BC,Ę McClearn GE.	Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains.	Alcohol Clin Exp Res	19(2)	367-373	Apr	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625571&dopt=Abstract	7625571	95351511	01	71-91 days	71	91	MF	17-41	g/kg	18.48		9.71		16.05		15.41		17.43		15.37		11.86		9.38		17.67		15.34		12.45		14.48				18.12		10.3						19.08		15.11				7.98		12.1		11.47		10.68		15.64				16.88		11.24																								7/11/2003	MK Sullivan		ETLORR4.1(PSU)	Acceptance	ACCEPT	EtOH	0.1		Rodriguez	p. 369, Table 1	MRG 120601 from publication	7625571.01
Alcohol acceptance - male raw mean consumption [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		02	74-91 days	74	91	Male	~50	g/kg body weight     					16.10		14.96		15.26		13.48		11.28		9.47		16.78		14.75		10.03		10.40				14.77		7.08		10.92				16.47		14.66				4.85		13.25		12.06		11.73		15.57		9.38		15.58		11.02																								6/5/2003	MK Sullivan	Nathan Copeland	ACCB alcohol acceptance									10581484.02
Alcohol acceptance - female raw mean consumption [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		03	74-91 days	74	91	Female	~50	g/kg body weight     					15.99		15.76		18.53		17.07		12.59		12.75		18.78		16.25		14.75		18.84				21.47		1351		15.41				18.35		15.70				10.10		13.48		10.88		9.63		17.43		12.82		18.18		11.05																								6/5/2003	MK Sullivan	Nathan Copeland	ACCB alcohol acceptance									10581484.03
Alcohol acceptance - male residual [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		01	74-91 days	74	91	Male	~50	g/kg body weight     					2.97		1.98		0.46		-0.36		0.39		-1.53		1.82		1.44		-2.28		-4.46				-1.97		-4.42		-1.83				1.78		1.72				-4.40		1.77		2.29		2.79		1.49		-1.67		1.00		1.15																								6/5/2003	MK Sullivan	Nathan Copeland	ACCB alcohol acceptance									10581484.01
Alcohol acceptance - female residual [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		04	74-91 days	74	91	Female	~50	g/kg body weight     					-1.54		-1.00		1.56		1.29		-1.72		-0.34		0.79		-0.37		1.28		5.12				4.83		2.02		1.35				0.58		-0.87				0.09		-2.14		-3.95		-4.98		0.26		-0.21		1.00		-3.08																								6/5/2003	MK Sullivan	Nathan Copeland	ACCB alcohol acceptance									10581484.04
Alcohol preference - female [g/kg]		Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.	Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE	Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains	Alcohol Clin Exp Res	18(6)	1416-1422	Dec	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695038&dopt=Abstract	7695038	95209059	03	50-70 days	50	70	Female	8-20	avg g/kg	16.92		2.64		5.56		6.51		4.59		8.03		4.28		3.33		4.98		4.81		2.4		3.2				9.61		4.06						4.7		4.29				3.15		7.95		8.39		6.63		3.91				10.49		2.19																								7/11/2003	MK Sullivan											7695038.03
Alcohol preference - male [g/kg]		Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.	Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE	Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains	Alcohol Clin Exp Res	18(6)	1416-1422	Dec	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695038&dopt=Abstract	7695038	95209059	04	50-70 days	50	70	Male	9-21	avg g/kg	12.84		2.07		3.32		3.65		3.68		4.69		4.98		2.64		5.05		5.2		2.03		2.15				4.08		2.18						4.57		3.73				2.34		7.25		6.37		6.84		5.06				8.04		2.32																								7/11/2003	MK Sullivan											7695038.04
alcohol preference - consumption of 10% ethanol vs. water over 15 days [g/kg]		Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (RI) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e), for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7), and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.	Rodriguez LA,Ę Plomin R,ĘBlizard DA,ĘJones BC,Ę McClearn GE.	Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains.	Alcohol Clin Exp Res	19(2)	367-373	Apr	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625571&dopt=Abstract	7625571	95351511	02	50-70 days	50	70	MF	18-41	g/kg	14.83		2.35		4.44		5.08		4.13		6.36		4.67		2.98		5.02		5		2.22		2.7				6.54		3.07						4.64		4.01				2.72		7.6		7.83		6.73		4.49				9.27		2.25																								7/11/2003	MK Sullivan		ACCB alcohol acceptance	Preference	PREFER	EtOH	0.1		Rodriguez	p. 369, Table 1	MRG 120601 from publication	7625571.02
Alcohol preference - male raw mean consumption [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		05	53-67 days	53	67	Male	~50	g/kg body weight     					3.31		3.60		3.68		4.66		3.82		2.68		5.75		4.82		1.97		2.27				4.09		2.22		4.43				4.46		3.68				2.22		6.54		5.64		5.53		5.04		3.01		8.01		2.37																								6/5/2003	MK Sullivan	Nathan Copeland										10581484.05
Alcohol preference - female raw mean consumption [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		06	53-67 days	53	67	Female	~50	g/kg body weight     					5.36		6.48		4.09		6.73		4.91		2.96		5.02		4.82		2.25		3.49				11.03		4.05		4.98				4.62		4.19				3.18		6.90		8.38		6.59		3.84		4.78		10.44		2.22																								6/5/2003	MK Sullivan	Nathan Copeland										10581484.06
Alcohol preference - male residual mean [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		07	53-67 days	53	67	Male	~50	g/kg body weight     					-0.81		-1.05		0.16		-0.10		-0.09		-0.31		1.79		0.96		-0.68		-0.97				-1.18		0.49		0.69				0.69		0.11				-0.88		1.70		0.10		0.83		1.64		-0.83		1.50		-0.27																								6/5/2003	MK Sullivan	Nathan Copeland										10581484.07
Alcohol preference - female residual mean [g/kg body weight]		During the past half century, researchers have identified and examined sex differences in alcohol-related phenotypes, focusing more recently on understanding of the mechanisms underlying these differences. In general, the genetic contributions influencing these differences are not consistent with an interpretation of sex linkage and must, therefore, reflect some form of sex limitation in which allelic differences at particular autosomal loci have different consequences in males and females. Significant sex differences in measures of alcohol consumption in mice have been demonstrated in previous work in our laboratory. To investigate these differences further, we explore the limiting case of sex-exclusive effects using data from (BXD) recombinant inbred (RI) strains of mice and from an intercross derived from the same progenitors, C57BL/6J (B) and DBA/2J (D). By the use of two statistical approaches (examination of residual scores as a sex-exclusive phenotypic value for the RI strains and multivariate regression on sex and genotype in the F(2)) we have identified and confirmed female-exclusive markers for alcohol acceptance on chromosomes 9 and 12 and one marker for alcohol preference on chromosome 2. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:647-652, 1999. Copyright 1999 Wiley-Liss, Inc.	Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE	Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes	Am J Med Genet 	88(6)	647-652	Dec	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10581484&dopt=Abstract	10581484		08	53-67 days	53	67	Female	~50	g/kg body weight     					0.88		1.70		-0.77		0.85		-0.10		-0.87		-1.98		-1.22		-0.85		0.09				5.75		0.70		-0.66				-1.05		-0.67				-0.17		-0.92		1.49		-0.18		-2.43		0.61		1.09		-1.29																								6/5/2003	MK Sullivan	Nathan Copeland										10581484.08
Antinociceptive responsiveness [%] 		Among inbred mouse strains, DBA/2 mice are unique because of their poor responsiveness to nitrous oxide (N2O) antinociception. As a first step towards identifying candidate genes involved in determining antinociceptive responsiveness to N2O, male mice from the DBA/2 strain, the more responsive C57BL/6 strain, their B6D2F1 offspring, and 22 BXD recombinant inbred (RI) strains derived from DBA/2 and C57BL/6 mice were exposed to N2O and evaluated using the acetic acid abdominal constriction test. When exposed to 70% N2O, C57BL/6, DBA/2 and B6D2F1 mice exhibited antinociceptive responses of 78, 22 and 55%, respectively. The BXD RI strains demonstrated varying degrees of responsiveness to N2O. Cluster analysis revealed one cluster of 16 strains approximating the C57BL/6 progenitor (61.9-100% antinociceptive response to 70% N2O) and another of six strains around the DBA/2 progenitor (9.1-40% antinociceptive response to 70% N2O). The robust strain differences permitted screening the strain means with 1492 marker loci previously mapped in BXD RI strains. Using a QTL analysis specifically tailored to existing mouse RI strains, we found associations at the 0.01 level on seven chromosomes with the most promising marker loci being Il2ra, Hbb, Hmg1rs7 and Gsl5 on chromosomes 2, 7, 16 and 19, respectively (P < 0.002).	Quock RM, Mueller JL, Vaughn LK, Belknap JK	Nitrous oxide antinociception in BXD recombinant inbred mouse strains and identification of quantitative trait loci.	Brain Research	725(1)	23-29	June	1996		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8828582&dopt=Abstract	8828582	96426288	01	6-7wks	42	49	Male	5	%	77		27		87		70		94				37		80		40		85		60		100		80		74				30				31		96				89		100		10		90		70		24		90		70																								6/10/2003	MK Sullivan											8828582.01
Audiogenic seizure susceptibility at 21 days [severity of seizure] 		Recombinant inbred (RI) strains are valuable not only for detecting major gene segregation and linkage but also for identifying associations between behavior and quantitative trait loci (QTL) that account for relatively small amounts of variation in behaviors for which strain distribution patterns are not bimodal. When applied to published data on genetic markers and on behavior for BXD RI strains, the RI QTL association approach suggests the presence of QTLs on chromosomes 6 and 12 for open-field activity and on chromosomes 1, 2, and 17 for high-pressure seizure susceptibility. Because the RI QTL approach does not require that the progenitor inbred strains of a particular RI series differ, researchers could focus on the BXD RI series, for which the greatest number of genetic markers are available. Focusing on BXD would capitalize on the cumulative nature of RI research which permits analyses of QTL sources of genetic correlations across studies.	Plomin R, McClearn GE, Gora-Maslak G,Ę Neiderhiser JM.	Use of recombinant inbred strains to detect quantitative trait loci associated with behavior.	Behav Genet	277(2)	99-116	Mar	1991		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2049054&dopt=Abstract	2049054	91264768	01	21 days	21				Severity of seizure; 0=no response, 1=wild running, 2=clonic seizure, 3=tonic seizure	.25		2.75		.25		2.25		2.25		.25		1.75		2.75		1.25		.25		.25		.25		2.75		.25				1.25				2.75				1.25		1.25		.25		1.75		1.25		.25		.25																												7/14/2003	MK Sullivan											2049054.01
Response to auditory stimulus US in contextualized fear conditioning paradigm [% freezing]		Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task.	Owen EH, Christensen SC, Paylor R, Wehner JM	Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.	Behav Neurosci 	111(2)	292-300	Apr	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9106670&dopt=Abstract	9106670	97260550	01	60-134 days 	60	134	MF	9-20	% freezing	70	5.62	60	5.46	62	5.38	45	7.15			20	4.38	51	7.62	60	5.23	100	1.23	40	6.62	64	6.38	32	5.00			18	4.54			20	5.23			67	8.62	61	3.90	64	3.77	41	9.15	50	5.92	53	5.77	61	5.31	64	6.54	62	5.38			65	4.62																							6/12/2003	MK Sullivan											9106670.01
Body weight [g]		PURPOSE: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped. METHODS: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J. RESULTS: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2. CONCLUSIONS: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.	Zhou G, Williams RW	Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse.	Invest Ophthalmol Vis Sci	40(5)	817-825	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102277&dopt=Abstract	10102277	99200400	01	106 days	106		MF	8-35	g	21.2		20.3		21.1		22.9		19.9		19.3		19.3		23.4		21		18.8		21.8		22.8		23.6		22		21		18.7		17.9		22.2		21.7		18.5		21.8		17.5		19.6		21.8		19		17.3		22.1		22																								6/12/2003	MK Sullivan											10102277.01
Brain methamphetamine levels after 8 mg/kg methamphetamine [micrograms/gm] 		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains.	J Neurosci	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	09	10-14 wks	70	98	MF	8	micrograms/gm	2	0.39	2.5	0.64	3.8	0.96	1.5	0.31	2.1	0.23	1.9	0.32	2.9	0.60	2.5	0.46	2.7	0.74	2.7	0.43	2.7	0.47	3.8	0.62	2.8	0.71	1.8	0.39	2.1	0.51	2.9	0.88			2.1	0.63	1.8	0.26	2.3	0.40	1.9	0.41	0.8	0.19	2	0.60	2.7	0.79	2	0.80	2.5	0.55	2.8	0.59	2.1	0.71																							6/4/2003	MK Sullivan											8987796.09
Brain weight [mg]		Common genetic polymorphisms-as opposed to rare mutations-generate almost all heritable differences in the size and structure of the CNS. Surprisingly, these normal variants have not previously been mapped or cloned in any vertebrate species. In a recent paper (), we suggested that much of the variation in retinal ganglion cell number in mice, and the striking bimodality of strain averages, are caused by one or two quantitative trait loci (QTLs). To test this idea, and to map genes linked to this variable and highly heritable quantitative trait, we have counted ganglion cells in 38 recombinant inbred strains (BXD and BXH) derived from parental strains that have high and low cell numbers. A genome-wide search using simple and composite interval-mapping techniques revealed a major QTL on chromosome (Chr) 11 in a 3 cM interval between Hoxb and Krt1 (LOD = 6.8; genome-wide p = 0.001) and possible subsidiary QTLs on Chr 2 and Chr 8. The Chr 11 locus, neuron number control 1 (Nnc1), accounts for one third of the genetic variance among BXH strains and more than half of that among BXD strains, but Nnc1 has no known effects on brain weight, eye weight, or total retinal cell number. Three strong candidate genes have been mapped previously to the same region as Nnc1. These genes-Rara, Thra, and Erbb2- encode receptors for retinoic acid, thyroxine, and neuregulin, respectively. Each receptor is expressed in the retina during development, and their ligands affect the proliferation or survival of retinal cells.	Williams RW, Strom RC., Goldowitz D 	Natural variation in neuron number in mice is linked to a major quantitative trait locus on Chr 11.	J Neurosci	18(1)	138-46	Jan	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9412494&dopt=Abstract	9412494	98075112	01	100 days	100		MF	5-11	mg	475		412		465		432		526		388		412		422		437		434		427		442		443		469		427		431		398		443		457		434		391		431		393		407		413		399		426		434																								6/18/2003	MK Sullivan											9412494.01
Brain weight [mg] [strains 33 to 42 calculated 6/28/00]		PURPOSE: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped. METHODS: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J. RESULTS: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2. CONCLUSIONS: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.	Zhou G, Williams RW	Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse.	Invest Ophthalmol Vis Sci	40(5)	817-825	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102277&dopt=Abstract	10102277	99200400	02	106 days	106		MF	8-35	mg	475		412		465		432		526		388		412		422		437		434		427		442		443		469		427		431		398		443		457		434		391		431		393		407		413		399		426		434		427.3		417.3		415.4		406.6		410.6		418.1		401.8		431.7				448.6				6/12/2003	MK Sullivan											10102277.02
Bronchial constrictor response- after exposure to atracurium [APTI (airway pressure time index)] [cmH2O.s]		Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of atopy and bronchial hyperresponsiveness. Recent studies localized a major gene for asthma to chromosome 5q31-q33 in humans. Thus, this segment of the genome represents a candidate region for genes that determine susceptibility to bronchial hyperresponsiveness and atopy in animal models. Homologs of candidate genes on human chromosome 5q31-q33 are found in four regions in the mouse genome, two on chromosome 18,Ęand one each on chromosomes 11Ęand 13.ĘWe assessed bronchial responsiveness as a quantitative trait in mice and found it linked to chromosome 13.ĘInterleukin 9Ę(IL-9) is located in the linked region and was analyzed as a gene candidate. The expression of IL-9 was markedly reduced in bronchial hyporesponsive mice, and the level of expression was determined by sequences within the qualitative trait locus (QTL). These data suggest a role for IL-9 in the complex pathogenesis of bronchial hyperresponsiveness as a risk factor for asthma. 	Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH, Levitt RC.	Interleukin 9: a candidate gene for asthma.	Proc Natl Acad Sci USA 	94(24)	13175-13180	Nov	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9371819&dopt=Abstract	9371819		01	5-6 wks	35	42	MF	2-13	cmH20.s	86	18	404	40	109	15	142	15	65	11	169	8	247	26	273	22	107	10	408	33	281	40	53	13	462	203	521	115	164	13	84	21			317	47	54	24			83	13	984	125	570	120	291	14	102	23	346	48	304	21	142	15																							6/11/2003	MK Sullivan	Nathan Copeland										9371819.01
Quiescent stem cells in old mice-cobblestone area forming cells (CAFC) day 35 frequency in bone marrow [105 BM cells]		To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequency of cobblestone area-forming cells (CAFC) day-35 in DBA fetal liver was twofold to threefold higher than in B6 mice, and by late gestation, the total stem cell number was nearly as large as that of young DBA adults. Following a further approximately 50% increase in stem cells between 6 weeks and 1 year of age, numbers in old DBA mice dropped precipitously between 12 and 20 months of age. In marked contrast, this stem cell population in B6 mice increased at a constant rate from late gestation to 20 months of age with no signs of abatement. Throughout development an inverse correlation was observed between stem cell numbers and the percentage of cells in S-phase. Because a strong genetic component contributed to the changes in stem cell numbers during aging, we quantified stem cells of 20-month old BXD recombinant inbred (RI) mice, derived from B6 and DBA progenitor strains, thus permitting detailed interstrain genetic analysis. For each BXD strain we calculated the stem cell increase or decrease as mice aged from 2 to 20 months. Net changes in CAFC-day 35 numbers among BXD strains ranged from an approximately 10-fold decrease to an approximately 10-fold increase. A genome-wide search for loci associated with this quantitative trait was performed. Several loci contribute to the trait-putative loci map to chromosomes X, 2, and 14. We conclude that stem cell numbers fluctuate widely during aging and that this has a strong genetic basis.	de Haan G, Van Zant G	Dynamic changes in mouse hematopoietic stem cell numbers during aging.	Blood	93(10)	3294-3301	May	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10233881&dopt=Abstract	10233881	99252083	01	2 months	60	62	Female		105 BM cells	1.5		3		1.5						2				3.5		8		2				3		2		2.5		2.5		2		2						2		2		1		2		3		0.5		3		3.3		3.5																								6/9/2003	MK Sullivan											10233881.01
Quiescent stem cells in aged mice-cobblestone area forming cells (CAFC) day 35 frequency in bone marrow [105 BM cells]		To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequency of cobblestone area-forming cells (CAFC) day-35 in DBA fetal liver was twofold to threefold higher than in B6 mice, and by late gestation, the total stem cell number was nearly as large as that of young DBA adults. Following a further approximately 50% increase in stem cells between 6 weeks and 1 year of age, numbers in old DBA mice dropped precipitously between 12 and 20 months of age. In marked contrast, this stem cell population in B6 mice increased at a constant rate from late gestation to 20 months of age with no signs of abatement. Throughout development an inverse correlation was observed between stem cell numbers and the percentage of cells in S-phase. Because a strong genetic component contributed to the changes in stem cell numbers during aging, we quantified stem cells of 20-month old BXD recombinant inbred (RI) mice, derived from B6 and DBA progenitor strains, thus permitting detailed interstrain genetic analysis. For each BXD strain we calculated the stem cell increase or decrease as mice aged from 2 to 20 months. Net changes in CAFC-day 35 numbers among BXD strains ranged from an approximately 10-fold decrease to an approximately 10-fold increase. A genome-wide search for loci associated with this quantitative trait was performed. Several loci contribute to the trait-putative loci map to chromosomes X, 2, and 14. We conclude that stem cell numbers fluctuate widely during aging and that this has a strong genetic basis.	de Haan G, Van Zant G	Dynamic changes in mouse hematopoietic stem cell numbers during aging.	Blood	93(10)	3294-3301	May	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10233881&dopt=Abstract	10233881	99252083	02	20 months	600	620	Female		105 BM cells	4		1		1						12				11.5		2		4.5				7		21		3.3		6		3.3		4						2.5		2.5		6		4		4		0.1		6.5		2		3.5																								6/9/2003	MK Sullivan											10233881.02
Chlordiazepoxide 10 mg/kg induced locomotor response distance traveled, 0-5 min time interval [cm] 		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	01	8-12 wks	56	84	Male	3-15	cm	-696	292	-81	123	-716	282			-40	182	-9	448	-284	391	197	163	919	668	112	156	-509	310	-594	250	216	233	7	239	668	276	335	299	744	295	76	115	787	282	-113	208	739	317	-39	304	-413	337	387	280	742	291	204	328	328	268	299	200																							6/6/2003	MK Sullivan											9880575.01
Chlordiazepoxide 10 mg/kg induced locomotor response distance traveled, 5-10 min time interval [cm] 		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	02	8-12wks	56	84	Male	3-15	cm	-459	253	863	307	-248	283			-487	209	-36	410	-18	446	-1623	286	1166	246	1306	119	-451	365	132	370	-1104	304	1377	407	10	431	-39	228	510	505	-246	299	-448	295	256	545	174	393	-86	294	-497	574	409	278	1909	316	-590	283	527	331	500	370																							6/6/2003	MK Sullivan											9880575.02
Chlordiazepoxide 10 mg/kg induced locomotor response distance traveled, 10-15 min time interval [cm] 		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	03	8-12wks	56	84	Male	3-15	cm	-69	352	875	219	-462	245			-846	231	-137	413	-285	269	-2600	262	518	381	477	773	-642	239	443	414	-1036	171	1013	337	266	372	-403	306	453	487	-520	255	-743	297	104	378	-390	370	-110	345	-555	658	9	170	903	362	-28	281	774	305	419	345																							6/6/2003	MK Sullivan											9880575.03
Chlordiazepoxide 10 mg/kg induced locomotor response distance traveled, 15-20 min time interval [cm] 		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	04	8-12wks	56	84	Male	3-15	cm	297	156	857	293	-817	248			-705	170	-358	318	-425	269	-2564	356	319	284	-383	707	-888	242	268	390	-835	359	814	387	367	347	-828	309	-40	420	-354	319	-622	335	825	552	-351	206	-132	365	-1058	181	-340	206	1059	399	-312	160	233	371	504	314																							6/6/2003	MK Sullivan											9880575.04
Chlordiazepoxide 10 mg/kg induced locomotor response distance traveled, 5-20 min time interval [cm]		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	05	8-12wks	56	84	Male	3-15	cm	-231	761	2595	819	-1526	776			-2039	610	-531	1141	-727	985	-6786	903	2002	911	1401	1600	-1981	846	843	1174	-2974	833	3204	1131	643	1149	-1270	843	923	1412	-1119	873	-1812	926	1185	1475	-567	969	-327	1005	-2110	1413	78	653	3870	1077	-930	724	1534	1007	1423	1030																							6/6/2003	MK Sullivan											9880575.05
Cerebellum weight [mg] 		To discover genes influencing cerebellum development, we conducted a complex trait analysis of variation in the size of the adult mouse cerebellum. We analyzed two sets of recombinant inbred BXD strains and an F2 intercross of the common inbred strains, C57BL/6J and DBA/2J. We measured cerebellar size as the weight or volume of fixed or histologically processed tissue. Among BXD recombinant inbred strains, the cerebellum averages 52 mg (12.4% of the brain) and ranges 18 mg in size. In F2 mice, the cerebellum averages 62 mg (12.9% of the brain) and ranges approximately 20 mg in size. Five quantitative trait loci (QTLs) that significantly control variation in cerebellar size were mapped to chromosomes 1 (Cbs1a), 8 (Cbs8a), 14 (Cbs14a), and 19 (Cbs19a, Cbs19b). In combination, these QTLs can shift cerebellar size an appreciable 35% of the observed range. To assess regional genetic control of the cerebellum, we also measured the volume of the cell-rich, internal granule layer (IGL) in a set of BXD strains. The IGL ranges from 34 to 43% of total cerebellar volume. The QTL Cbs8a is significantly linked to variation in IGL volume and is suggestively linked to variation in the number of cerebellar folia. The QTLs we have discovered are among the first loci shown to modulate the size and architecture of the adult mouse cerebellum.	Airey DC, Lu L, Williams RW.	Genetic control of the mouse cerebellum: identification of quantitative trait loci modulating size and architecture.	J Neurosci	21(14)	5099-5109	Jul	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11438585&dopt=Abstract	11438585		01	30-300 days	30	300	MF	4-7	mg					61.4	2.38	49.0	1.25	62.5	2.32	53.1	1.22	59.1	2.07	53.9	1.05	53.1	1.10	45.9	1.09	48.4	1.63	49.4	0.44	47.4	1.15	56.3	1.21	53.6	1.44	50.1	1.42	48.2	1.67	50.6	1.31	53.8	1.51	48.6	1.03	54.9	1.92	49.6	0.81	47.4	2.25	51.5	0.87	50.2	0.56	53.6	1.14	49.7	0.91	56.0	1.19	52.1	0.66	53.7	1.22	49.7	2.03	44.5	0.73			51.1	1.79	54.9	0.87	49.9	1.13			59.4	0.95			12/20/2002												11438585.01
Stem cell cycling - change in day 7 cobblestone area forming cell (CAFC) frequency during aging [%CAFC]		To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequency of cobblestone area-forming cells (CAFC) day-35 in DBA fetal liver was twofold to threefold higher than in B6 mice, and by late gestation, the total stem cell number was nearly as large as that of young DBA adults. Following a further approximately 50% increase in stem cells between 6 weeks and 1 year of age, numbers in old DBA mice dropped precipitously between 12 and 20 months of age. In marked contrast, this stem cell population in B6 mice increased at a constant rate from late gestation to 20 months of age with no signs of abatement. Throughout development an inverse correlation was observed between stem cell numbers and the percentage of cells in S-phase. Because a strong genetic component contributed to the changes in stem cell numbers during aging, we quantified stem cells of 20-month old BXD recombinant inbred (RI) mice, derived from B6 and DBA progenitor strains, thus permitting detailed interstrain genetic analysis. For each BXD strain we calculated the stem cell increase or decrease as mice aged from 2 to 20 months. Net changes in CAFC-day 35 numbers among BXD strains ranged from an approximately 10-fold decrease to an approximately 10-fold increase. A genome-wide search for loci associated with this quantitative trait was performed. Several loci contribute to the trait-putative loci map to chromosomes X, 2, and 14. We conclude that stem cell numbers fluctuate widely during aging and that this has a strong genetic basis.	de Haan G, Van Zant G	Dynamic changes in mouse hematopoietic stem cell numbers during aging.	Blood	93(10)	3294-3301	May	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10233881&dopt=Abstract	10233881	99252083	03	2-20 months	61	610	Female	3-8	%	110		100		125						110				102		98		105				125		75		110		110		102		104						103		120		100		104		105		90		120		85		80																								6/9/2003	MK Sullivan											10233881.03
Change in day 21 cobblestone area forming cell (CAFC) frequency during aging [% CAFC]		To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequency of cobblestone area-forming cells (CAFC) day-35 in DBA fetal liver was twofold to threefold higher than in B6 mice, and by late gestation, the total stem cell number was nearly as large as that of young DBA adults. Following a further approximately 50% increase in stem cells between 6 weeks and 1 year of age, numbers in old DBA mice dropped precipitously between 12 and 20 months of age. In marked contrast, this stem cell population in B6 mice increased at a constant rate from late gestation to 20 months of age with no signs of abatement. Throughout development an inverse correlation was observed between stem cell numbers and the percentage of cells in S-phase. Because a strong genetic component contributed to the changes in stem cell numbers during aging, we quantified stem cells of 20-month old BXD recombinant inbred (RI) mice, derived from B6 and DBA progenitor strains, thus permitting detailed interstrain genetic analysis. For each BXD strain we calculated the stem cell increase or decrease as mice aged from 2 to 20 months. Net changes in CAFC-day 35 numbers among BXD strains ranged from an approximately 10-fold decrease to an approximately 10-fold increase. A genome-wide search for loci associated with this quantitative trait was performed. Several loci contribute to the trait-putative loci map to chromosomes X, 2, and 14. We conclude that stem cell numbers fluctuate widely during aging and that this has a strong genetic basis.	de Haan G, Van Zant G	Dynamic changes in mouse hematopoietic stem cell numbers during aging.	Blood	93(10)	3294-3301	May	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10233881&dopt=Abstract	10233881	99252083	04	2-20 months	61	610	Female	3-8	%	180		82		90						200				120		80		125				130		340		108		130		92		130						115		70		110		110		108		60		125		75		108																								6/9/2003	MK Sullivan											10233881.04
Quiescent stem cells - change in day 35 CAFC frequency during aging [% CAFC]		To address the fundamental question of whether or not stem cell populations age, we performed quantitative measurements of the cycling status and frequency of hematopoietic stem cells in long-lived C57BL/6 (B6) and short-lived DBA/2 (DBA) mice at different developmental and aging stages. The frequency of cobblestone area-forming cells (CAFC) day-35 in DBA fetal liver was twofold to threefold higher than in B6 mice, and by late gestation, the total stem cell number was nearly as large as that of young DBA adults. Following a further approximately 50% increase in stem cells between 6 weeks and 1 year of age, numbers in old DBA mice dropped precipitously between 12 and 20 months of age. In marked contrast, this stem cell population in B6 mice increased at a constant rate from late gestation to 20 months of age with no signs of abatement. Throughout development an inverse correlation was observed between stem cell numbers and the percentage of cells in S-phase. Because a strong genetic component contributed to the changes in stem cell numbers during aging, we quantified stem cells of 20-month old BXD recombinant inbred (RI) mice, derived from B6 and DBA progenitor strains, thus permitting detailed interstrain genetic analysis. For each BXD strain we calculated the stem cell increase or decrease as mice aged from 2 to 20 months. Net changes in CAFC-day 35 numbers among BXD strains ranged from an approximately 10-fold decrease to an approximately 10-fold increase. A genome-wide search for loci associated with this quantitative trait was performed. Several loci contribute to the trait-putative loci map to chromosomes X, 2, and 14. We conclude that stem cell numbers fluctuate widely during aging and that this has a strong genetic basis.	de Haan G, Van Zant G	Dynamic changes in mouse hematopoietic stem cell numbers during aging.	Blood	93(10)	3294-3301	May	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10233881&dopt=Abstract	10233881	99252083	05	2-20 months	61	610	Female	3-8	%	190		75		103						420				190		50		130				130		800		108		130		110		125						110		108		240		125		110		20		135		80		102																								6/9/2003	Mk Sullivan											10233881.05
Circadian Period		Many genes support the manifestation of the circadian period in mice. In a multiple-gene trait all genes contributing in a minor way to this characteristic are quantitative trait loci (QTL). Screens of both the BXD and the CXB panels of recombinant inbred mice suggested that distal chromosome 1, between 90 and 100 cM, contained a QTL, Cplaq3, for a difference in the circadian period of locomotor activity between the C57BL/6J and the DBA/2J and between the BALB/cBy and the C57BL/6By progenitor strains. The mice studied were a commercially available congenic strain, B6.D2-Mtv7a/Ty, from 50 to 100 days old. This congenic strain contains a small DBA/2J genomic insert that covers the region of the provisional QTL in a 99.9% C57BL/6J background. The congenic mice had a shorter period than C57BL/6J mice, confirming that this region has a QTL for the difference in period between the C57BL/6J and the DBA/2J strains. In addition, these data suggest that this region has a QTL for the mean amount of daily activity and for the pattern of locomotor activity.	Mayeda AR,        Hofstetter JR	A QTL for the genetic variance in free-running period and level of locomotor activity between inbred strains of mice.	Behav Genet	29(3)	171-176	May	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10547923&dopt=Abstract	10547923	20015646	01	100 days	100																																																																																			6/6/2002												10547923.01
Climbing scores after 16 mg/kg i.p. methamphetamine injection [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains.	J Neurosci	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	10	10-14 wks	70	98	MF	8	quadrant crossings/min	2.3	0.22	0.6	0.28	0.1	0.45	-0.8	0.31	1.5	0.39	-0.8	0.38	0.3	0.32			-0.1	0.21	0.7	0.47	2.6	0.30	-1	0.48	-0.7	0.23	2	0.43	-0.3	0.29	0.4	0.39			0.1	0.17	3.3	0.21	0.7	0.39	0.8	0.51	0.6	0.35	0.6	0.38	1	0.40	-1.4	0.30	2.6	0.14	-0.8	0.48	1.6	0.34																							6/4/2003	MK Sullivan											8987796.1
Response to contextual fear [% freezing]		Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task.	Owen EH, Christensen SC, Paylor R, Wehner JM	Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.	Behav Neurosci 	111(2)	292-300	Apr	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9106670&dopt=Abstract	9106670	97260550	02	60-134 days 	60	134	MF	9-20	% freezing	38	0.431	15	0.238	23	5.38	23	5.00			10	1.85	29	10.62	10	2.54	38	5.77	10	2.69	38	5.08	10	2.38			23	5.00			11	3.77			23	5.08	35	3.46	50	4.77	20	3.00	15	3.83	40	3.08	38	3.00	5	1.77	23	2.77			45	5.00																							6/12/2003	MK Sullivan											9106670.02
Decrease in body temp after TNF injection [degree C]		Administration of recombinant murine tumor necrosis factor (TNF) to mice results in lethal shock, characterized by hypotension, hypothermia, and dramatic induction of cytokines released in the circulation, such as interleukin-6 (IL-6). The sensitivity of mice to the effects of murine TNF varies from strain to strain. DBA/2 mice were found to be considerably more resistant to TNF than C57BL/6 mice. The resistance proved to be dominant since (C57BL/6 x DBA/2)F1 mice were also resistant. Using BXD recombinant inbred mice and a dose of TNF lethal for C57BL/6 but not for DBA/2 mice, we found that the resistance to TNF links to loci coding for corticosteroid-binding globulin (Cbg), alpha1-protease inhibitor (Spi1), contrapsin (Spi2) and the contrapsin-regulating gene Spi2r that form a gene cluster on chromosome 12. Quantitative trait-loci analysis of TNF-induced induction of IL-6 and of hypothermia also points to the importance of this locus (P < 0.0002 and P = 0.017, respectively), more particularly the Cbg and Spi2 loci, in the resistance to TNF. We propose to name the locus "TNF protection locus." The data suggest that endogenous protease inhibitors and/or glucocorticoids play a significant role in the attenuation of TNF-induced lethal shock. This study also demonstrates that loci affecting important biological responses can be identified with very high resolution using recombinant inbred mice.	Libert C,ĘWielockx B, Hammond GL,Ę Brouckaert P,ĘFiers W,ĘElliott RW.	Identification of a locus on distal mouse chromosome 12 that controls resistance to tumor necrosis factor-induced lethal shock.	Genomics	55(3)	284-289	Feb	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10049582&dopt=Abstract	10049582	99168897	01	15 wks	105		Female	2-9	degree C	26.3	2.21	35.1	0.27	30.1	0.59	26.2	1.69			35.4	0.15	35.5	0.18	31.9	0.63	35.6	0.11					31.3	0.94	33.3	0.96	34.5	0.31					23.6	0.58	31.6	0.75	30.4	0.84	30.2	0.25	35.6	0.16	35.4	0.23	31.2	0.56	31.6	0.12			27.2	0.49	26	1.20	34.2	0.78																					35.7	0.15	6/9/2003	MK Sullivan											10049582.01
Pentylenetetrazol (PTZ) induced seizure thresholds [mg/kg]		Gene mapping of the newly discovered SEZ genes (seizure-related genes) in the mouse was performed by linkage analysis. SEZ6 was on chromosome 11, SEZ12 on chromosome 16, SEZ15 on chromosome 3 and SEZ17 (PTZ17) on chromosome 18. The mouse chromosomal locus related to high susceptibility to pentylenetetrazol (PTZ) was also determined by linkage analysis using the recombinant inbred mouse, BXD (C57BLxDBA). A significant level of PTZ susceptibility was found on chromosome 2. Chromosomal loci of the newly discovered SEZ genes were not coincident with the significant chromosomal loci to PTZ susceptibility. Since epilepsy is assumed to be a disease syndrome which is probably manifested by abnormal expression of multifocal genes, determination of the role of each chromosomal locus in the provocation of seizure activity is important.	Wakana S, Sugaya E, Naramoto F, Yokote N, Maruyama C, Jin W, Ohguchi H, Tsuda T, Sugaya A, Kajiwara K.	Gene mapping of SEZ group genes and determination of pentylenetetrazol susceptible quantitative trait loci in the mouse chromosome.	Brain Res	857(1-2)	286-290	Feb	2000		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10700579&dopt=Abstract	10700579		01						mg/kg	35	7.1	23	2.5	30	4.2	41	4.3	28	2.7	40	7.9			25	2.5	37	2.9	32	4.7	28	3.0	27	3.9			33	2.4	31	1.5	30	0.0			29	6.4	29	3.4	29	3.4	28	2.4	29	3.4			32	5.2	34	2.8	38	4.5	33	3.2	27	3.3																							6/6/2002		Nathan Copeland										10700579.01
Imprinting - egg modifier phenotypes [% androgen development]		It is now well established that genomic imprinting effects in mammals require a combination of epigenetic modifications imposed during gametogenesis and additional modifications imposed after fertilization. The earliest post-fertilization modifications to be imposed on the genome are those thought to be mediated by factors in the egg cytoplasm. Strain-dependent differences in the actions of these egg modifiers in mice reveal an important potential for genetic variability in the imprinting process, and also provide valuable genetic systems with which to identify some of the factors that participate in imprinting. Previous studies documented a strain-dependent difference in the modification of paternal genome function between the C57BL/6 and DBA/2 mouse strains. This difference is revealed as a difference in developmental potential of androgenetic embryos produced with eggs from females of the two strains by nuclear transplantation. The specificity of the effect for the paternal genome is consistent with an effect on imprinted genes. The egg phenotype is largely independent of the genotype of the fertilizing sperm, and the C57BL/6 phenotype is dominant in reciprocal F1 hybrids. Genetic studies demonstrated that the difference in egg phenotypes between the two strains is most likely controlled by two independently segregating loci. We now report the results of experiments in which the egg phenotypes of the available BxD recombinant inbred mouse strains have been determined. The results of the analysis are consistent with the two locus model, and we have identified candidate chromosomal locations for the two loci. These data demonstrate clearly that differences in how the egg cytoplasm modifies the incoming paternal genome are indeed genetically determined, and vary accordingly.	Latham KE, Sapienza C.	Localization of genes encoding egg modifiers of paternal genome function to mouse chromosomes one and two.	Development 	125(5)	929-935	Mar	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9449675&dopt=Abstract	9449675		01				Female		%					41		56		23		52		41		50		57		8				46		39		62		71		32		27		10		61		51		46		64		61		44		20		64		49		63																								6/6/2002		Nathan Copeland										9449675.01
Ethanol induced locomotor response distance traveled, 0-5 min time interval [cm] 		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	06	8-12wks	56	84	Male	4-18	cm	208	321	2284	261	1274	516			323	413	-208	364	1182	324	289	370	308	265	1819	347	925	291	146	375	943	341	1845	410	2042	447	1786	338	1423	389	1228	250	481	269	109	420	683	560	698	403	447	266	486	126	155	600	983	495	414	325	1073	289																							6/6/2003	MK Sullivan		ETBethanol									9880575.06
Ethanol induced locomotor response distance traveled, 5-10 min time interval [cm]		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	07	8-12wks	56	84	Male	4-18	cm	536	330	1689	353	533	283			-144	293	-504	420	1387	322	-2024	460	459	213	2298	279	392	306	288	224	-119	132	1884	351	2243	436	264	402	2291	437	1904	361	-1116	257	-138	318	-281	444	-378	558	1689	528	566	142	1038	253	902	424	671	216	515	296																							6/6/2003	MK Sullivan		ETBethanol									9880575.07
Ethanol induced locomotor response distance traveled, 10-15 min time interval [cm]		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	08	8-12wks	56	84	Male	4-18	cm	356	331	1094	233	182	265			-824	280	-1115	348	1344	318	-2458	169	599	249	1244	141	282	199	-354	416	-324	158	1555	427	2235	367	-357	444	1742	498	1693	339	-591	233	-450	260	-319	336	-634	355	800	368	749	203	799	325	758	315	908	301	766	391																							6/6/2003	MK Sullivan		ETBethanol									9880575.08
Ethanol induced locomotor response distance traveled, 15-20 min time interval [cm]		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	09	8-12wks	56	84	Male	4-18	cm	215	232	739	207	639	336			-936	270	-1376	316	1147	309	-2107	151	578	280	1495	188	-308	296	-857	304	-420	133	1416	422	1799	299	-606	424	1234	241	1406	323	-528	233	-173	248	-380	293	-711	375	319	396	515	269	142	369	1065	211	1225	200	851	238																							6/6/2003	MK Sullivan		ETBethanol									9880575.09
Ethanol induced locomotor response distance traveled, 5-20 min time interval [cm]		A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).	Demarest K,ĘMcCaughran J,ĘMahjubi E,ĘCipp L,ĘHitzemann R.	Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2.	J Neurosci	19(2)	549-561	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9880575&dopt=Abstract	9880575	99098941	10	8-12wks	56	84	Male	4-18	cm	1107	893	3522	793	1354	884			-1905	843	-2995	1083	3879	950	-6588	779	1636	743	5037	608	366	800	-923	944	-864	423	4855	1200	6277	1102	-717	1271	5267	1175	5003	1023	-2235	724	-761	826	-979	1073	-1722	1288	2808	1293	1829	614	1980	947	2725	951	2805	716	2132	924																							6/6/2003	MK Sullivan		ETBethanol									9880575.1
Eye weight [mg] [strains 33 to 42 calculated 6/28/00]		PURPOSE: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped. METHODS: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J. RESULTS: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2. CONCLUSIONS: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.	Zhou G, Williams RW	Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse.	Invest Ophthalmol Vis Sci	40(5)	817-825	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102277&dopt=Abstract	10102277	99200400	03	106 days	106		MF	8-35	mg	18.9	0.2	20.2	0.2	20.1	0.4	20.1	0.2	19.6	0.3	19.7	0.3	18.7	0.3	19.4	0.3	20.3	0.3	18.9	0.2	18.2	0.3	18.3	0.2	19.1	0.3	19.3	0.1	17.3	0.4	20.1	0.2	19.4	0.2	15.6	0.4	19.3	0.2	18.4	0.2	16.3	0.3	16.8	0.3	19.2	0.2	17.5	0.2	19.4	0.3	17.8	0.5	20	0.3	20	0.3	F										19.5												6/12/2003	MK Sullivan											10102277.03
Forebrain weight [mg] [raw average from strainDB 6/28/00]			Williams RW unpub		unpublished				2000					82	100 days	100		MF		mg																	300.8		295.4		288.4		311.1		323.4		331.2		316.3				275.0		323.9		322.8		288.5		295.2		286.3		260.9		282.7		277.9		257.2		293.4		311.2																								12/19/2002												.82
Ethanol induced conditioned place preference - Grid floor preference after 2 g/kg ethanol i.p. paired with grid [s/min]	table 3 col 1	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	10	56-125 days	56	125	Male	6-17	s/min	35.6	1.9	36.0	2.5	43.7	2.8	40.9	2.0	32.1	2.3	38.6	2.5	36.2	2.0	36.1	2.5	50.5	2.9	35.7	2.5	33.7	2.8	35.7	2.1	36.1	2.9	40.5	5.0	34.5	1.7					31	1.7	36.3	4.9			45.7	2.9	33.8	1.7	43.5	3.0	31.2	2.9	34.5	1.5																													6/23/2003	MK Sullivan											7480533.1
Ethanol induced conditioned place preference - Hole floor preference after 2 g/kg ethanol i.p. paired with hole floor [s/min]	table 3 col 2	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	11	56-125 days	56	125	Male	7-17	s/min	25.6	2.3	24.4	3.5	26.0	2.9	25.8	3.7	26.6	2.5	22.8	2.5	22.5	2.0	24.0	1.9	16.0	3.3	26.1	2.8	22.1	2.0	29.4	2.4	19.4	2.2	26.4	4.0	253	2.0					31.5	1.7	17.4	3.8			16.2	3.1	33.7	1.8	23.0	3.9	25.7	3.2	30.5	1.8																													6/23/2003	MK Sullivan											7480533.11
High Affinity Choline Uptake (concentration of 0.5*10^-6M) in frontal cortex [pmole/4min/mg protein]		Using the quantitative trait loci (QTL) approach, preliminary identification has been made of a region on mouse chromosome 17 that influences high-affinity choline uptake (HACU) in the mouse brain. The rate of HACU was measured in synaptosomes prepared from the frontal cortex, hippocampus, and striatum of C57BL/6J (B6), DBA/2J (D2), and 25 BXD recombinant inbred (RI) strains of mice, using a final concentration of 0.5 microM [3H]choline. The strain means of HACU in each area were then correlated with the strain distribution pattern of each of 1300 known genetic markers using a point biserial correlation and 0 (B6 allele) and 1 (D2 allele). Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1. Correlations of P < 0.0001 were found between striatal HACU and chromosome 17 markers D17Leh66e, D17Leh119, D17Rp17e, Plg, D17Leh66d, Ckb-rs2, and Trp53-ps. QTL analyses of HACU in the frontal cortex and hippocampus also revealed correlations with these markers at the level of P < 0.05 and P < 0.01. These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse.	Tarricone BJ, Hwang WG, Hingtgen JN, Mitchell SR, Belknap JK, Nurnberger JI	Identification of a locus on mouse chromosome 17 associated with high-affinity choline uptake using BXD recombinant inbred mice and quantitative trait loci analysis	Genomics	27(1)	161-164	May	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7665164&dopt=Abstract	7665164	95394453	01	12-14 wks	84	98	Male	4	pmole/4min/mg protein	17.2	1.8	13.1	1.1	18.5	1.8	17.3	2.2	13.7	1.4	15.4	0.9	25	1.3	22.1	1.5	12.8	1.9	17.8	1.7	25.5	2.6	19	5.5	24.4	2.4	17.3	2.0	18.2	2.1	24.9	3.0			23.4	3.0	16.4	1.2	26.8	4.5	19.3	4.1	23.7	2.2	17.3	2.0	21.2	0.4	20.5	1.9	18.7	1.2	12.5	2.0	25.9	1.7																							6/11/2003	MK Sullivan											7665164.01
High Affinity Choline Uptake (concentration of 0.5*10^-6M) in hippocampus [pmole/4min/mg protein]		Using the quantitative trait loci (QTL) approach, preliminary identification has been made of a region on mouse chromosome 17 that influences high-affinity choline uptake (HACU) in the mouse brain. The rate of HACU was measured in synaptosomes prepared from the frontal cortex, hippocampus, and striatum of C57BL/6J (B6), DBA/2J (D2), and 25 BXD recombinant inbred (RI) strains of mice, using a final concentration of 0.5 microM [3H]choline. The strain means of HACU in each area were then correlated with the strain distribution pattern of each of 1300 known genetic markers using a point biserial correlation and 0 (B6 allele) and 1 (D2 allele). Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1. Correlations of P < 0.0001 were found between striatal HACU and chromosome 17 markers D17Leh66e, D17Leh119, D17Rp17e, Plg, D17Leh66d, Ckb-rs2, and Trp53-ps. QTL analyses of HACU in the frontal cortex and hippocampus also revealed correlations with these markers at the level of P < 0.05 and P < 0.01. These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse.	Tarricone BJ, Hwang WG, Hingtgen JN, Mitchell SR, Belknap JK, Nurnberger JI	Identification of a locus on mouse chromosome 17 associated with high-affinity choline uptake using BXD recombinant inbred mice and quantitative trait loci analysis	Genomics	27(1)	161-164	May	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7665164&dopt=Abstract	7665164	95394453	02	12-14 wks	84	98	Male	4	pmole/4min/mg protein	17.5	1.5	14.2	1.2	17.6	1.6	18.9	1.7	22.4	1.5	18.9	1.4	20.8	3.4	25.9	2.4	21.2	2.3	19.9	0.9	27.7	4.0	22.2	1.5	23.3	2.4	17.4	1.4	19.1	1.4	28.5	2.7			25.2	3.3	21.6	1.8	26.2	3.2	17.9	2.6	36	3.0	21	2.6	22.4	1.2	30.3	3.4	22.8	1.6	17.7	5.7	23.6	4.8																							6/11/2003	MK Sullivan											7665164.02
High Affinity Choline Uptake (concentration of 0.5*10^-6M) in striatum [pmole/4min/mg protein]		Using the quantitative trait loci (QTL) approach, preliminary identification has been made of a region on mouse chromosome 17 that influences high-affinity choline uptake (HACU) in the mouse brain. The rate of HACU was measured in synaptosomes prepared from the frontal cortex, hippocampus, and striatum of C57BL/6J (B6), DBA/2J (D2), and 25 BXD recombinant inbred (RI) strains of mice, using a final concentration of 0.5 microM [3H]choline. The strain means of HACU in each area were then correlated with the strain distribution pattern of each of 1300 known genetic markers using a point biserial correlation and 0 (B6 allele) and 1 (D2 allele). Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1. Correlations of P < 0.0001 were found between striatal HACU and chromosome 17 markers D17Leh66e, D17Leh119, D17Rp17e, Plg, D17Leh66d, Ckb-rs2, and Trp53-ps. QTL analyses of HACU in the frontal cortex and hippocampus also revealed correlations with these markers at the level of P < 0.05 and P < 0.01. These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse.	Tarricone BJ, Hwang WG, Hingtgen JN, Mitchell SR, Belknap JK, Nurnberger JI	Identification of a locus on mouse chromosome 17 associated with high-affinity choline uptake using BXD recombinant inbred mice and quantitative trait loci analysis	Genomics	27(1)	161-164	May	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7665164&dopt=Abstract	7665164	95394453	03	12-14 wks	84	98	Male	4	pmole/4min/mg protein	80.1	5.7	64.8	5.9	52.4	4.6	62.8	7.0	43.5	4.0	55.5	8.0	112.1	13.9	94.2	14.4	59.4	6.6	54.7	7.2	92.3	23.3	90.4	13.6	112.8	10.0	62.7	2.2	55.2	4.7	107.1	11.3			89.3	7.8	59.5	4.2	107.9	10.2	51.7	3.4	128.9	4.8	76.2	4.7	78.1	4.1	79.2	7.6	51.6	3.2	52.5	4.1	87.2	9.6																							6/11/2003	MK Sullivan											7665164.03
Haloperidol induced catalepsy - ED50 [mg/kg]		The strain means for haloperidol-induced catalepsy were determined in the 26 strain BXD recombinant inbred series. The ED50 values ranged from 0.55 mg/kg (strain 30) to 7.9 mg/kg (strain 2). Heritability for the catalepsy response was 0.78 and the number of effective loci was estimated to be four. The strain means were correlated with the strain distribution patterns for 1300 marker loci of known chromosomal location and polymorphic between the C57Bl/6J and DBA/2J strains. Six quantitative trait loci (QTLs) were identified at P < .01. Two of the six QTLs were confirmed in a sample of B6XD2 F2 animals (n = 144), phenotyped for haloperidol response and genotyped for microsatellites closely linked to the QTLs. The confirmed QTL on chromosome 4 is near the b locus. The confirmed QTL on chromosome 9 is closely linked to Drd2, the D2 dopamine receptor gene. One hundred of the F2 individuals were phenotyped for D2 dopamine receptor binding using the ligand [125I] epidepride as the ligand. Consistent with previous results, the nonresponsive F2 individuals showed modestly higher receptor binding in all brain regions examined: the nucleus accumbens core, the nucleus accumbens shell, the lateral caudate putamen, the dorsomedial caudate putamen, the substantia nigra zona compacta and the ventral tegmental area. The DBA/2J allele of the chromosome 9 QTL was associated with higher receptor binding in all brain areas except the ventral tegmental area. Overall, the data illustrate that either near or part of Drd2 is a QTL which has significant effects on both haloperidol response and D2 dopamine receptor binding. However, the data also illustrate that most of the genetic variance in either haloperidol response or D2 dopamine receptor binding is not associated with Drd2.	Kanes S, Dains K	Mapping the genes for haloperidol-induced catalepsy.	J Pharmacol Exp Ther	277(2)	1016-1025	May	1996		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627512&dopt=Abstract	8627512	96210104	01	100 days	100		MF		mg/kg	3.8		0.4		1.17		7.9		1.23		3.25		1.48		1.73		2.47		2.94		1.53		2.31		1.17		4.18		4.43		2.39		2.8		0.98		0.61		5.89		0.93		3.62		1.35		2.73		6.67		0.55		0.96		3.81																								6/6/2002												8627512.01
High Dose Sensitivity to ethanol sleep time female [min]		Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.	Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE	Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains	Alcohol Clin Exp Res	18(6)	1416-1422	Dec	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695038&dopt=Abstract	7695038	95209059	05	117-137 days	117	137	Female	7-15	min	103.83		116.46		109.89		121.93		17.96		112.66		125.27		97.84		107.41		159.76		91.98		119.62				104.52								100.89		132.81				110.6		115.38		111.68		116.27		119.97				146.8		141.16																								7/11/2003	MK Sullivan											7695038.05
High Dose Sensitivity to ethanol sleep time male [min]		Although the recombinant inbred strain method was designed for molecular genetic analysis of linkage, it also provides powerful quantitative genetic analyses of heritability and genetic correlations. Measures of alcohol acceptance, alcohol preference, and hypnotic dose sensitivity (HDS) were assessed in 21 strains of mice from the BXD RI series. Sex differences were found to be significant at a phenotypic level. However, heritability estimates for acceptance, preference, and HDS are similar in males and females. Heritability estimates for the three measures are approximately 0.20 for acceptance and preference, and 0.10 for HDS. Analyses of genetic correlations reveal that acceptance and preference share some degree of genetic influence, although they mostly operate under different genetically mediated mechanisms. HDS did not show a significant genetic relationship to either acceptance or preference. Strong correlations were obtained when acceptance, preference, and HDS strain means were correlated across male and female recombinant inbreds, suggesting substantial genetic similarity across sexes.	Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE	Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains	Alcohol Clin Exp Res	18(6)	1416-1422	Dec	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695038&dopt=Abstract	7695038	95209059	06	117-137 days	117	137	Male	7-17	min	118.43		108.61		116.96		142.79		150.8		136.34		126.14		109.79		109.32		157.56		125		105.96				140.48								103.54		153.76				129.67		145.67		128.02		109.74		128.2				141.96		154.62																								7/11/2003	MK Sullivan											7695038.06
High Dose Sensitivity to ethanol - Duration (mins) of loss of righting reflex following 4.1 g/kg EtOH i.p.		Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (RI) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e), for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7), and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.	Rodriguez LA,Ę Plomin R,ĘBlizard DA, Jones BC,Ę McClearn GE.	Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains	Alcohol Clin Exp Res	19(2)	367-373	Apr	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625571&dopt=Abstract	7625571	95351511	03	117-137days	117	137	MF	15-31	min	112.1		112.41		113.21		132.36		139.98		124.5		125.7		103.5		108.37		158.71		110.55		112.39				118.9								102.21		144.6				120.13		127.85		119.85		113		124.08				144.54		148.24																								7/11/2003	MK Sullivan		ETCONS10(PSU)	HDS	HDS           High Dose Sensitivity	EtOH	4.1 g/kg		Rodriguez	p. 369, Table 1	MRG 120601 from publication	7625571.03
Hemopoietic stem cell cycling day 7 [% CAFC]		Normal somatic cells undergo replicative senescence in vitro but the significance of this process in organismic aging remains controversial. We have shown previously that hemopoietic stem cells of common inbred strains of mice vary widely in cycling activity and that this parameter is inversely correlated with strain-dependent mean life span. To assess whether cell cycling and life span are causally related, we searched for quantitative trait loci (QTLs) that contributed to variation of these traits in BXH and BXD recombinant inbred mice. Two QTLs, mapping to exactly the same intervals on chromosomes 7 and 11, were identified that were associated with variation of both cell cycling and life span. The locus on chromosome 11 mapped to the cytokine cluster, a segment that shows synteny with human chromosome 5q, in which deletions are strongly associated with myelodysplastic syndrome. These data indicate that steady-state cell turn-over, here measured in hemopoietic progenitor cells, may have a significant effect on the mean life span of mammals.	de Haan G, Van Zant G                                                                                                                                                                                                                                                                                                                                                                                                              	Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span.	FASEB J	13(6)	707-713	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10094931&dopt=Abstract	10094931	99196952	01	6-8 wks	42	56	Female	10-20	%	8	10.4	20	9.8	36	10.6	12.6	11.1	31	9.7	31	7.8	13	10.8	2	7.6	29	7.6	16	8.3	26	6.3	18	8.9	22	9.0	34	8.6	13	6.1	2	11.5	0.8	11.2	32	9.6	6	6.8	12.6	12.0	7.8	12.8	0.8	7.6	12.8	11.1	24	8.7	19	6.1	0.8	9.4	56	3.3	34	8.9																							6/9/2003	MK Sullivan											10094931.01
Hindbrain weight [mg] [raw average from strainDB 6/28/00]			Williams RW unpub		unpublished				2000					81	100 days	100		MF		mg																	42.5		46.5		42.0		43.4		39.1		44.1		44.7		43.1		34.3		36.2		42.6		41.8		46.3		39.2		30.8		44.4		41.5		38.6		43.6		50.1																								12/19/2002												.81
Hippocampus weight [raw average from strainDB 6/28/00]		Notable differences in hippocampal structure are associated with intriguing differences in development and behavioral capabilities. We explored genetic and environmental factors that modulate hippocampal size, structure, and cell number using sets of C57BL/6J (B6) and DBA/2J (D2) mice; their F1 and F2 intercrosses (n = 180); and 35 lines of BXD recombinant inbred (RI) strains. Hippocampal weights of the parental strains differ by 20%. Estimates of granule cell number also differ by approximately 20%. Hippocampal weights of RI strains range from 21 to 31 mg, and those of individual F2 mice range from 23 to 36 mg (bilateral weights). Volume and granule cell number are well correlated (r = 0.7-0.8). Significant variation is associated with differences in age and sex. The hippocampus increases in weight by 0.24 mg per month, and those of males are 0.55 mg heavier (bilateral) than those of females. Heritability of variation is approximately 50%, and half of this genetic variation is generated by two quantitative trait loci that map to chromosome 1 (Hipp1a: genome-wide p < 0.005, between 65 and 100 cM) and to chromosome 5 (Hipp5a, p < 0.05, between 15 and 40 cM). These are among the first gene loci known to produce normal variation in forebrain structure. Hipp1a and Hipp5a individually modulate hippocampal weight by 1.0-2.0 mg, an effect size greater than that generated by age or sex. The Hipp gene loci modulate neuron number in the dentate gyrus, collectively shifting the population up or down by as much as 200,000 cells. Candidate genes for the Hipp loci include Rxrg and Fgfr3.	Lu L, Airey DC, Williams RW	Complex trait analysis of the hippocampus: mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice.	J Neurosci	21(10)	3503-3514	May	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11331379&dopt=Abstract	11331379		01	100 days	100		MF							27.1		25.3		26.8		26.3		26.2		25.4		25.5		26.4		24.7		26.0		27.9		28.3		26.2		28.3		24.3		26.5		25.3		24.3		23.9		24.5		23.3		23.1		22.1		21.1		23.6		25.3		26.3		23.8		26.1		25.7		24.5		27.3		24.7		30.5				27.4				12/20/2002												11331379.01
Induction of serum IL-6 after TNF injection [ng/ml]		Administration of recombinant murine tumor necrosis factor (TNF) to mice results in lethal shock, characterized by hypotension, hypothermia, and dramatic induction of cytokines released in the circulation, such as interleukin-6 (IL-6). The sensitivity of mice to the effects of murine TNF varies from strain to strain. DBA/2 mice were found to be considerably more resistant to TNF than C57BL/6 mice. The resistance proved to be dominant since (C57BL/6 x DBA/2)F1 mice were also resistant. Using BXD recombinant inbred mice and a dose of TNF lethal for C57BL/6 but not for DBA/2 mice, we found that the resistance to TNF links to loci coding for corticosteroid-binding globulin (Cbg), alpha1-protease inhibitor (Spi1), contrapsin (Spi2) and the contrapsin-regulating gene Spi2r that form a gene cluster on chromosome 12. Quantitative trait-loci analysis of TNF-induced induction of IL-6 and of hypothermia also points to the importance of this locus (P < 0.0002 and P = 0.017, respectively), more particularly the Cbg and Spi2 loci, in the resistance to TNF. We propose to name the locus "TNF protection locus." The data suggest that endogenous protease inhibitors and/or glucocorticoids play a significant role in the attenuation of TNF-induced lethal shock. This study also demonstrates that loci affecting important biological responses can be identified with very high resolution using recombinant inbred mice.	Libert C,ĘWielockx B, Hammond GL,Ę Brouckaert P,ĘFiers W,ĘElliott RW.	Identification of a locus on distal mouse chromosome 12 that controls resistance to tumor necrosis factor-induced lethal shock.	Genomics	55(3)	284-289	Feb	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10049582&dopt=Abstract	10049582	99168897	02	15 wks	105		Female	2-9	ng/ml	5	0.49	2.45	0.12	4	0.20	5.3	0.42			2.5	0.34	3	0.17	2.9	0.40	2.5	0.19					5.5	0.21	2.95	0.14	2.55	0.40					4.4	0.23	4.25	0.15	4.8	0.28	5	0.40	1.8	0.03	2.5	0.12	2.8	0.10	3	0.50			4.3	0.33	4.9	0.45	1.7	0.07																					2.2	0.10	6/9/2003	MK Sullivan											10049582.02
Prepulse Inhibition of the Acoustic Startle Response to 110 dB SPL white-noise bursts, 5 kHz, 80 dB Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	08	100 days	100		MF	9-15	%	50.8		24.4		31.6				34.8		17.5		36.3		40.7		9.9				35.3		-6.7		14.2		12.3				34.1						16		39.5		-14.6		19		11.6		19		31.5		-9.9		14.9		-10.4																								12/27/2002	Ryan McNeive	Ryan McNeive										10371755.08
Prepulse Inhibition of the Acoustic Startle Response to 110 dB SPL white-noise bursts, 10 kHz,80 dB Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	09	100 days	100		MF	9-15	%	62.9		42.2		46.6				40.2		15.8		45.9		49.3		38				37.8		12.5		17.4		6.2				43.1						16.7		24.8		-2.7		27.4		20.6		39.1		37.5		-1		19.8		4.2																								12/27/2002	Ryan McNeive	Ryan McNeive										10371755.09
Prepulse Inhibition of the Acoustic Startle Response to 110 dB SPL white-noise bursts, 15 kHz, 80 dB Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	10	100 days	100		MF	9-15	%	46		45.9		40.8				54.7		25.5		27		37.5		33.3				25.6		-1.9		-10.6		6.6				22.4						15.6		59.4		17.1		41		4.5		29.8		46.2		14.8		18.8		-6.6																								12/27/2002	Ryan McNeive	Ryan McNeive										10371755.1
Prepulse Inhibition of the Acoustic Startle Response to 110 dB SPL white-noise bursts, 20 kHz, 80 dB Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	11	100 days	100		MF	9-15	%	40.6		9.2		31.6				23		15.3		13.6		21.7		25.7				11.8		-9.7		8.8		-7.3				7.1						9.6		31.9		-6.3		0.2		2.7		13.2		32.2		-2.6		13.1		-3.4																								12/27/2002	Ryan McNeive	Ryan McNeive										10371755.11
Prepulse Inhibition of the Acoustic Startle Response to a 110-db SPL, 10 kHz tone, 56-db SPL white-noise Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	12	100 days	100		MF	9-15	%	26.8		2.1		44				25.9		13.4		60.1		35.7		13.3		35.4		30.4		27.9		13.7		9.8		59.5		8.4				44.7		36.2				15.1		39.1		4.9		25.1		3.4		35.8		15.2		17.8																								12/27/2002	Ryan McNeive	Ryan McNeive										10371755.12
Prepulse Inhibition of the Acoustic Startle Response to a 110-db SPL, 10 kHz tone, 68-db SPL white-noise Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	13	100 days	100		MF	9-15	%	32.8		15.5		53				30.5		15.2		65.3		31.5		14.2		21.4		35.2		33.8		18.1		12.9		57.9		28.4				40.6		51				24.2		39.8		13		38		18.3		38.6		28.5		25.8																								6/6/2002	Ryan McNeive	Ryan McNeive										10371755.13
Prepulse Inhibition of the Acoustic Startle Response to a 110-db SPL, 10 kHz tone, 80-db SPL white-noise Prepulse Stimulus [%] 		The measurement of the acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR in many inbred strains of mice, including C57BL/6 and DBA/2, may be complicated by age-related high-frequency hearing loss (HFHL) and the associated cochlear pathology. Willott and Erway (1998) have recently reported on the age-related changes of the acoustic brain response in the BXD recombinant inbred (RI) series. Based on these data, the RI series was divided into three groups: juvenile-, intermediate-, and adult-onset HFHL. Each of these groups was tested using paradigms which varied the frequency or intensity of the auditory startle and prepulse stimuli. The results obtained in adolescent mice (6-8 weeks) demonstrate that ASR performance is independent of HFHL; there was no group-dependent decline in the ASR amplitudes for high-frequency stimuli. The expected effect of HFHL on PPI is to increase the salience of the still-audible tones. In response to a white-noise prepulse stimulus, the PPI in the juvenile-onset group (which shows marked HFHL at 6 weeks) was similar to that in the adult-onset group. However, when the prepulse stimulus was a pure tone, the juvenile group showed a decrease in salience across all frequencies tested (5-20 kHz). The data point out the need for carefully constructing auditory tasks in the BXD RI series, to avoid the confounding effects of HFHL.	McCaughran J, Bell J, Hitzemann R	On the relationships of high-frequency hearing loss and cochlear pathology to the acoustic startle response (ASR) and prepulse inhibition of the ASR in the BXD recombinant inbred series	Behav Genet	29(1)	21-30	Jan	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10371755&dopt=Abstract	10371755	99300343	14	100 days	100		MF	9-15	%	42.9		22.6		62.4				29.4		30.1		75.1		33.4		35.9		32.8		46.2		37.5		25.6		21.8		58.5		34.4				7.9		48.7				36.4		50.6		21.7		55.6		14.2		37.5		42.3		42.9																								6/6/2002	Ryan McNeive	Ryan McNeive										10371755.14
Initial sensitivity to ethanol induced ataxia, onset threshold [mg/kg]		Rapid tolerance to rotarod ataxia has previously been demonstrated in mice after sequential ethanol injections. Here we tested DBA/2J and C57BL/6J mice for initial ethanol sensitivity; DBA/2J mice were more sensitive (0.40 +/- 0.17 mg/g brain) than C57BL/6J mice (1.44 +/- 0.12 mg/g). We then monitored the development of tolerance by quantifying blood ethanol concentrations at the recovery from ataxia over five sequential injections; tolerance reached a plateau in about 5 hr. DBA/2J mice became very tolerant (final ethanol threshold 3.47 +/- 0.16 mg/ml, an increase of 3.07 mg/ml, or 8.7-fold above base line); B6 became slightly tolerant (final ethanol threshold 2.62 +/- 12 mg/ml, and increase of 1.18, or 1.8-fold above base line). Therefore, by the end of the treatment regimen, the rank order of sensitivity of the two strains had reversed. We then tested 25 recombinant inbred strains from among strains representing a cross between C57BL/6J and DBA/2J inbred strains, followed by a quantitative trait locus analysis with a database of 1522 markers to identify provisional loci. This procedure identified 19 markers on 11 chromosomes for initial sensitivity, 18 markers on 9 chromosomes for tolerance (delta) and 21 markers on 11 chromosomes for tolerance (fold-increase). Of these, 17 markers were in common, which suggests that initial sensitivity and tolerance share substantial genetic codetermination. Major candidate loci will be confirmed by genotyping B6D2F2 offspring that have been tested for initial sensitivity and tolerance.	Gallaher EJ, Jones GE	Mapping the genes for haloperidol-induced catalepsy.	J Pharmacol Exp Ther	277(2)	604-612	May	1996		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627537&dopt=Abstract	8627537	96210104	01	44-135 days	44	135	Male	4-16	mg/kg	1.44		0.4		1.21		1.09		0.8		1.03		0.77		1.16		0.88		0.94		0.71		0.8		0.41		1.22		1.28		0.98				1.07		0.49		0.9		0.72		1.07		0.8		0.69		1.37		1.03		1.15		0.44																								12/19/2002												8627537.01
Intensity of Immune complex deposits detected in kidneys immunized with the 16/6Id [0=no immune complexes; 1=1 - 5 immune complex deposits; 2=5 - 20 immune complaex deposits; 3=20 - 50 immune complex depostits; 4=50 immune complex depostis]		The DBA/2 and C57BL/6 mouse strains, as well as the BXD RI lines derived from these strains, were used to map the genes controlling experimentally induced systemic lupus erythematosus (SLE). SLE was induced using two immunologic approaches: (1) immunization with the human monoclonal anti-DNA antibody expressing the 16/6Id, to which the DBA/2 strain is susceptible (responder) and the C57BL/6 strain is resistant (nonresponder); and (2) induction of autoimmune GVHD in B6D2F1 hosts by inoculation of parental DBA/2 (induces SLE) or C57BL/6 (does not induce SLE) T cells. By both approaches the BXD RI lines could be divided into distinct DBA/2-like and C57BL/6-like categories. Concordance of SLE induced by both methods was observed for susceptibility and resistance in 13/15 BXD lines (P < 0.005). The results suggest that at least two non-H-2 genes control susceptibility and resistance to experimentally induced SLE, one mapping to chromosome 7 and the other mapping to chromosome 14.	Mozes E, Alling D, Miller MW, Payne SM, Zinger H, Via CS, Shearer GM.	Genetic analysis of experimentally induced lupus in mice.	Clin Immunol Immunopathol	85(1)	28-34	Oct	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9325066&dopt=Abstract	9325066		01	6-8 wks	42	56	MF	5-10	0=no immune complexes; 1=1 - 5 immune complex deposits; 2=5 - 20 immune complaex deposits; 3=20 - 50 immune complex depostits; 4=50 immune complex depostis	0		3		0		3		2		0				2		3		0		0		4		0		0		0						0		1				0		2																																				6/6/2003	MK Sullivan	Nathan Copeland										9325066.01
Lens weight [mg]		PURPOSE: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped. METHODS: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J. RESULTS: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2. CONCLUSIONS: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.	Zhou G, Williams RW	Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse.	Invest Ophthalmol Vis Sci	40(5)	817-825	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102277&dopt=Abstract	10102277	99200400	04	106 days	106		MF	8-35	mg	5.9		6.7		6.2		6.1		5.7		5.9		5.8		6		6		5.3		5.3		5.7		5.7		6.1		5.2		6.5		5.5		4.8		6		5.5		5.3		5.3		5.6		5		5.9		5.5		6		6.2																								6/12/2003	MK Sullivan											10102277.04
Lethality due to TNF injection [%]		Administration of recombinant murine tumor necrosis factor (TNF) to mice results in lethal shock, characterized by hypotension, hypothermia, and dramatic induction of cytokines released in the circulation, such as interleukin-6 (IL-6). The sensitivity of mice to the effects of murine TNF varies from strain to strain. DBA/2 mice were found to be considerably more resistant to TNF than C57BL/6 mice. The resistance proved to be dominant since (C57BL/6 x DBA/2)F1 mice were also resistant. Using BXD recombinant inbred mice and a dose of TNF lethal for C57BL/6 but not for DBA/2 mice, we found that the resistance to TNF links to loci coding for corticosteroid-binding globulin (Cbg), alpha1-protease inhibitor (Spi1), contrapsin (Spi2) and the contrapsin-regulating gene Spi2r that form a gene cluster on chromosome 12. Quantitative trait-loci analysis of TNF-induced induction of IL-6 and of hypothermia also points to the importance of this locus (P < 0.0002 and P = 0.017, respectively), more particularly the Cbg and Spi2 loci, in the resistance to TNF. We propose to name the locus "TNF protection locus." The data suggest that endogenous protease inhibitors and/or glucocorticoids play a significant role in the attenuation of TNF-induced lethal shock. This study also demonstrates that loci affecting important biological responses can be identified with very high resolution using recombinant inbred mice.	Libert C,ĘWielockx B, Hammond GL,Ę Brouckaert P,ĘFiers W,ĘElliott RW.	Identification of a locus on distal mouse chromosome 12 that controls resistance to tumor necrosis factor-induced lethal shock.	Genomics	55(3)	284-289	Feb	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10049582&dopt=Abstract	10049582	99168897	03	15 wks	105		Female	2-9	%	100		0		79		100		66		0		0		12		0				0		89		0		20		56		75		100		100		89		100		10		0		10		20				100		83		10																								6/9/2003	MK Sullivan											10049582.03
Locomotor activity, 1 - 5 min habituation after single saline i.p. injection (experimental group) [activity/min]	table 1 col 1	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	12	56-125 days	56	125	Male	13-34	activity counts/min	116.2	5.5	65.1	5.8	116.0	5.7	83.7	6.1	54.9	6.0	106.7	7.8	47.4	2.1	76.6	5.6	50.4	4.1	91.5	6.3	60	3.1	97.6	8.6	53	2.4	48.3	1.9	87.1	4.1					52.1	1.9	48.4	3.7			47.3	2.5	85.8	6.6	49.9	7.1	44.5	3.4	146.4	6.8																													6/23/2003	MK Sullivan											7480533.12
Locomotor activity, 1 - 5 min after saline (experimental group trial 1) [activity counts per min]	table 1 col 2	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	13	56-125 days	56	125	Male	13-34	activity counts/min	87.8	4.8	63.7	3.3	92.4	3.6	73.5	6.0	40.4	1.7	82.3	3.9	48.1	2.6	73.6	4.4	45.7	2.6	66	4.7	46.3	2.7	66.6	4.0	45.9	1.9	45.7	1.4	83.5	4.0					53.6	1.6	47	2.0			38.8	2.7	8.7	3.9	60.1	5.6	51.9	3.8	143.6	4.5																													6/23/2003	MK Sullivan			Saline: Trial 1								7480533.13
Locomotor activity, 1 - 5 min after saline i.p., trial 4 (experimental group, prior Ethanol exposure) [activity counts per min]	table 1 col 3	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	04	56-125 days	56	125	Male	13-34	activity counts/min	39.9	1.9	53.5	4.6	54.6	3.6	36.9	3.9	27.3	1.6	40.4	2.9	29.7	2.6	52.8	3.4	24.1	1.9	33.8	3.5	23.8	2.0	42.7	2.8	37.6	2.0	28.2	1.4	68.8	4.0					47.6	2.4	35.7	2.6			32.4	2.9	49.8	3.1	34	4.4	37.8	4.5	124.7	6.1																													6/23/2003	MK Sullivan			Saline: Trial 4								7480533.04
Locomotor activity, 1 - 5 min after 2 g/kg ethanol i.p. conditioning trial 1 [activity counts per min]	table 1 col 4	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	05	56-125 days	56	125	Male	13-34	2 g/kg IP, activity counts/min	116.7	8.0	138.9	8.8	134.6	9.3	93.7	4.3	76.8	2.6	97.8	4.6	134	7.1	122.6	4.4	98.1	7.2	68.1	5.2	89.4	5.9	124.6	7.5	64.1	3.8	60.7	3.4	128.0	6.3					104.2	6.0	80.0	4.9			67.0	4.6	150.7	9.7	98.6	11.3	75.3	4.5	175	6.7																													6/23/2003	MK Sullivan											7480533.05
Locomotor activity, 1 -5 min after 2 g/kg ethanol IP conditioning trial 4 (experimental group prior ethanol exposure) [activity counts per min]	table 1 col 5	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	15	56-125 days	56	125	Male	13-34	2 g/kg IP, activity counts/min	57.6	4.1	165.8	7.2	90.4	9.8	67.6	4.9	54.4	4.0	50.4	3.7	123.7	10.5	138.5	7.8	61.0	6.0	45.1	4.9	70.1	7.3	94.5	7.9	49.0	3.5	31.7	2.7	126.0	7.3					114.3	8.7	77.3	4.3			74.3	5.8	115.8	10.1	133.4	12.3	59.3	5.7	170.8	9.1																													6/23/2003	MK Sullivan											7480533.15
Locomotor activity, 1 - 5 min after single saline i.p. injection (control group) [activity/min]	table 2 col 1	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	07	56-125 days	56	125	Male	6-16	activity/min	132.9	7.5	66.0	7.2	101.1	7.0	77.5	10.8	57	7.1	117.9	9.0	52.1	3.6	85.7	10.7	50.2	6.0	87	7.5	68.1	8.6	80.6	10.7	47.4	4.3	44.8	4.0	93.1	7.5					56.3	4.0	46.1	6.9			46.9	2.7	81.8	10.3	54.3	7.5	49	3.5	141.7	9.7																													6/23/2003	MK Sullivan											7480533.07
Locomotor activity, 1 - 5 min after saline i.p., trial 1 (control group) [activity/min]	table 2 col 2	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	08	56-125 days	56	125	Male	6-16	activity/min	75.9	5.7	48.0	4.6	74.4	4.8	58.5	6.0	35.2	2.1	81.0	6.4	50.6	2.9	67.5	4.6	37.2	3.8	60.4	6.0	37.1	2.6	52.2	4.2	44.5	3.2	37.8	2.2	75.9	3.9					57.2	2.0	45.0	3.5			35.4	2.1	62.8	4.2	58.3	9.4	41.2	3.5	135.0	6.8																													6/23/2003	MK Sullivan			Saline: Trial 1								7480533.08
Locomotor activity, 1 - 5 min after saline i.p., trial 4 (control group) [activity/min]	table 2 col 3	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	09	56-125 days	56	125	Male	6-16	activity/min	37.8	3.4	39.3	5.0	41.9	3.4	26.4	3.2	22.9	2.2	38.7	4.9	28.6	3.4	41.2	3.6	14.9	2.2	35.9	4.5	15.4	2.0	33.9	3.7	33.6	2.5	25.5	1.8	58.2	4.1					41.6	2.4	30.2	4.2			20.5	3.8	36.8	3.3	22.1	3.4	30.2	4.1	97.5	8.2																													6/23/2003	MK Sullivan			Saline: Trial 4								7480533.09
Maximal threshold  to ethanol induced ataxia [mg/ml] 		Rapid tolerance to rotarod ataxia has previously been demonstrated in mice after sequential ethanol injections. Here we tested DBA/2J and C57BL/6J mice for initial ethanol sensitivity; DBA/2J mice were more sensitive (0.40 +/- 0.17 mg/g brain) than C57BL/6J mice (1.44 +/- 0.12 mg/g). We then monitored the development of tolerance by quantifying blood ethanol concentrations at the recovery from ataxia over five sequential injections; tolerance reached a plateau in about 5 hr. DBA/2J mice became very tolerant (final ethanol threshold 3.47 +/- 0.16 mg/ml, an increase of 3.07 mg/ml, or 8.7-fold above base line); B6 became slightly tolerant (final ethanol threshold 2.62 +/- 12 mg/ml, and increase of 1.18, or 1.8-fold above base line). Therefore, by the end of the treatment regimen, the rank order of sensitivity of the two strains had reversed. We then tested 25 recombinant inbred strains from among strains representing a cross between C57BL/6J and DBA/2J inbred strains, followed by a quantitative trait locus analysis with a database of 1522 markers to identify provisional loci. This procedure identified 19 markers on 11 chromosomes for initial sensitivity, 18 markers on 9 chromosomes for tolerance (delta) and 21 markers on 11 chromosomes for tolerance (fold-increase). Of these, 17 markers were in common, which suggests that initial sensitivity and tolerance share substantial genetic codetermination. Major candidate loci will be confirmed by genotyping B6D2F2 offspring that have been tested for initial sensitivity and tolerance.	Gallaher EJ, Jones GE	Mapping the genes for haloperidol-induced catalepsy.	J Pharmacol Exp Ther	277(2)	604-612	May	1996		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627537&dopt=Abstract	8627537	96210104	02	44-135 days	44	135	Male	5-12	mg/ml	2.62		3.47		3.75		2.94		2.75		2.21		3.13		3.63		3.24		2.63		3.27		2.65		2.66		2.88		2.86		2.81				2.93		3.28		3.12		3.26		3.17		2.67		3.21		2.91		3.52		2.57		3.49																								12/19/2002												8627537.02
Mean life span [longevity in days] 		Normal somatic cells undergo replicative senescence in vitro but the significance of this process in organismic aging remains controversial. We have shown previously that hemopoietic stem cells of common inbred strains of mice vary widely in cycling activity and that this parameter is inversely correlated with strain-dependent mean life span. To assess whether cell cycling and life span are causally related, we searched for quantitative trait loci (QTLs) that contributed to variation of these traits in BXH and BXD recombinant inbred mice. Two QTLs, mapping to exactly the same intervals on chromosomes 7 and 11, were identified that were associated with variation of both cell cycling and life span. The locus on chromosome 11 mapped to the cytokine cluster, a segment that shows synteny with human chromosome 5q, in which deletions are strongly associated with myelodysplastic syndrome. These data indicate that steady-state cell turn-over, here measured in hemopoietic progenitor cells, may have a significant effect on the mean life span of mammals.	de Haan G, Van Zant G	Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span.	FASEB J	13(6)	707-713	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10094931&dopt=Abstract	10094931	99196952	02	6-8 wks	42	56	Female	10-20	days	675		175		600		400		525		690		660		825		750		740				500		800		650		740		900						740		760		840				715		760		700		740		580		200																								6/9/2003	MK Sullivan											10094931.02
Medulla weight [mg] [mean value calculated 6/29/00]			Williams RW unpub		unpublished				2000					80	100 days	100		MF		mg											5.5		8.2		8.6										6.8						5.7				7.3																						6.3		6.3		5.9		5.7				6.4		6.4		7.2				7.0				12/19/2002												.8
Mossy fiber MF		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	01	100 days	100		MF			201035		170534		235457		183237		176552		204155		241324		183084		167761		168565		182073		208777		181884		166098		166098		195597		183097		195597		167891		169252		159822		169252		159888		195822		183649		172789		206713		159736																								6/6/2002												8024533.01
Mossy fiber CA4MF		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	02	100 days	100		MF			95604		73495		108113		79558		69461		98145		102257		82676		76052		71343		80200		85196		91529		84975		72329		78205		80195		82715		77941		79350		69893		72158		67393		86697		81027		73771		89044		70752																								6/6/2002												8024533.02
Mossy fiber SPMF		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	03	100 days	100		MF			78388		93765		101833		83695		82143		92057		105625		84840		76814		75664		84697		98555		118355		77463		72642		93293		77409		92860		90151		79737		77537		75635		74170		85185		83292		83211		98742		74437																								6/6/2002												8024533.03
Mossy fiber IIPMF		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	04	100 days	100		MF			27042		12275		25512		19984		24948		13953		33443		15568		14895		21558		17176		25025		14859		19446		21127		12645		7688		20021		15005		26597		20462		21460		18326		24939		19329		15807		18926		14546																								6/6/2002												8024533.04
Mossy fiber CA4/MF %		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	05	100 days	100		MF			47.56		40.88		45.42		43.33		39.48		48.17		42.3		45.26		45.36		42.32		44.08		40.6		40.6		46.77		43.53		42.64		48.55		42.21		42.57		42.66		41.82		42.65		42.2		43.74		44.11		42.72		42.64		44.29																								6/6/2002												8024533.05
Mossy fiber SP/MF %		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	06	100 days	100		MF			39.03		52.37		43.77		45.94		46.47		45.06		43.77		46.39		45.85		44.97		46.61		47.62		52.8		42.62		43.77		50.57		46.88		47.69		49.27		43.05		46.2		44.73		46.5		43.68		45.41		48.17		48.16		46.67																								6/6/2002												8024533.06
Mossy fiber IIP/MF %		Mice of the BALB/c strain are widely used in behavioral research in spite of the albino condition, which can obscure brain-behavior relationships. We have developed a pigmented BALB strain, congenic to BALB/c, which could be more appropriate for neurogenetic studies that aim at identifying the effects of neurological mutations on behavior. Comparison of inbred albino and pigmented congenic BALB arising from the same litters provides a valuable tool for detecting the consequences of the albino mutation on behavioral performances. Preliminary results presented here show that the albino condition does not interfere with the development and patterns of connectivity of mossy fibers in the hippocampus. On the other hand, obvious coat color-linked differences appear for locomotor activity and defecation scores in the open field, pigmented mice being unexpectedly less active and more reactive than albino, as if better vision increased their reactions to a novel, anxiogenic environment. Finally, pigmented mice do not show better performances in the radial maze, which confirms that the inability of BALB mice for spatial learning in a highly demanding version of this task cannot be attributed to their inability to process visual information.	Lassalle JM,ĘHalley H,ĘRoullet P.	Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice.	Behav Genet	24(2)	161-169	Mar	1994		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8024533&dopt=Abstract	8024533	94296355	07	100 days	100		MF			13.41		6.76		10.81		10.73		14.05		6.77		13.93		8.34		8.79		12.71		9.31		11.78		6.6		10.61		12.7		6.78		4.57		10.1		8.16		14.29		11.97		12.62		11.31		12.58		10.48		9.11		9		9.04																								6/6/2002												8024533.07
Lavageable bronchoalveolar polymorphonuclear leukocytes (PMNs) 6h after acute (3h) exposure to 2ppm ozone, number of PMNs [BAL (x10^3)]		We demonstrated previously that inbred strains of mice are differentially susceptible to acute (3 h) and subacute (48 h) exposures to 2 parts per million (ppm) ozone (O3) and 0.30 ppm O3, respectively. Genetic studies with O3-resistant C3H/HeJ and O3-susceptible C57BL/6J strains have indicated that susceptibility to each of these O3 exposures is under Mendelian (single gene) control. In the present study, we hypothesized that the same gene controls susceptibility to the airway inflammatory responses to 2 ppm and 0.30 ppm O3 exposures. To test this hypothesis, airway inflammation was induced in 10 BXH and 16 BXD recombinant inbred (RI) strains of mice by acute as well as subacute O3 exposures. Airway inflammation was assessed by counting the number of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage (BAL) returns obtained immediately after 48-h subacute exposure to 0.30 ppm O3, or 6 h after 3 h acute exposure to 2 ppm O3. Each RI strain was classified as susceptible or resistant to each exposure, based on a comparison of mean numbers of PMNs with those of the respective progenitor strains. For each RI set, a phenotypic strain distribution pattern (SDP) was thus derived for each exposure regimen, and the SDPs were then compared for concordance. Among the BXH RI strains, 4 of 10 responded discordantly to the two exposures: 3 were susceptible to acute exposure and resistant to subacute exposure, whereas 1 was conversely susceptible. Among the BXD RI strains, 4 of 16 were discordant: 1 was susceptible to acute exposure, and resistant to subacute exposure, whereas 3 were conversely susceptible.(ABSTRACT TRUNCATED AT 250 WORDS)	Kleeberger SR, Levitt RC, Zhang LY.	Susceptibility to ozone-induced inflammation. II. Separate loci control responses to acute and subacute exposures	Am J Physiol	264(1Pt 1)	L21-L26	Jan	1993		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8430813&dopt=Abstract	8430813		01	6-8 wks	42	56	MF	4-38	number of PMNs in BAL (x103)	10	1.4	2	1.3	2	1.3	4	1.8					2	1.4	1	1.3	13	1.9	2	1.4							1	1.4							15	5.1					3	1.6	2	1.6	23	6.5	1	1.5	1	1.3	2	1.2	1	1.3	1	1.6																							6/25/2003	MK Sullivan											8430813.01
Lavageable bronchoalveolar polymorphonuclear leukocytes (PMNs) 6h after subacute (48h) exposure to 0.30 ppm ozone, number of PMNs [BAL (x10^3)]		We demonstrated previously that inbred strains of mice are differentially susceptible to acute (3 h) and subacute (48 h) exposures to 2 parts per million (ppm) ozone (O3) and 0.30 ppm O3, respectively. Genetic studies with O3-resistant C3H/HeJ and O3-susceptible C57BL/6J strains have indicated that susceptibility to each of these O3 exposures is under Mendelian (single gene) control. In the present study, we hypothesized that the same gene controls susceptibility to the airway inflammatory responses to 2 ppm and 0.30 ppm O3 exposures. To test this hypothesis, airway inflammation was induced in 10 BXH and 16 BXD recombinant inbred (RI) strains of mice by acute as well as subacute O3 exposures. Airway inflammation was assessed by counting the number of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage (BAL) returns obtained immediately after 48-h subacute exposure to 0.30 ppm O3, or 6 h after 3 h acute exposure to 2 ppm O3. Each RI strain was classified as susceptible or resistant to each exposure, based on a comparison of mean numbers of PMNs with those of the respective progenitor strains. For each RI set, a phenotypic strain distribution pattern (SDP) was thus derived for each exposure regimen, and the SDPs were then compared for concordance. Among the BXH RI strains, 4 of 10 responded discordantly to the two exposures: 3 were susceptible to acute exposure and resistant to subacute exposure, whereas 1 was conversely susceptible. Among the BXD RI strains, 4 of 16 were discordant: 1 was susceptible to acute exposure, and resistant to subacute exposure, whereas 3 were conversely susceptible.(ABSTRACT TRUNCATED AT 250 WORDS)	Kleeberger SR, Levitt RC, Zhang LY.	Susceptibility to ozone-induced inflammation. II. Separate loci control responses to acute and subacute exposures	Am J Physiol	264(1Pt 1)	L21-L26	Jan	1993		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8430813&dopt=Abstract	8430813		02	6-8 wks	42	56	MF	2-16	number of PMNs in BAL (x103)	10	2.1	2	1.3	14	3.5	16	4.5					14	4.9	1	1.3	23	6.9	1	1.3							4	1.3							2	1.3					2	1.5	2	1.3	14	2.0	1	1.4	2	1.4	2	1.4	1	1.3	1	1.3																							6/25/2003	MK Sullivan											8430813.02
T cell receptor expression,  V-gamma-1 positive, V-gamma-4 positive, % of total gamma-delta intestinal intraepithelial lymphocytes [%]		Most of the gd T cells in the intestinal epithelium of normal mice use the Vg1 or the Vg7 gene segments. However, the relative proportions of  gd intraepithelial lymphocytes expressing either the Vg1 or the Vg7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gd T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vg1, Vg4, Vg7, and Vd4 to examine the TCR repertoire of intraepithelial gd lymphocytes in a set of (C57BL/6Ę´ĘDBA/2) recombinant inbred strains. Our results show that the representation of different Vg and Vd gene products among gd   intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRg, TCRd, and major histocompatibility complex loci. 	Pereira P, Lafaille JJ, Gerber D, and Tonegawa S	The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility 	Proc Natl Acad Sci USA	94(11)	5761-5766	May	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9159147&dopt=Abstract	9159147		01	2-6 months	60 	180	MF	2	% 					14.75 		1.5 		3.25		4.75 		4.25		6.25 		2.25		10.75 		8.75		7.5		2.25 		2.75		8.75		1.5 				2.75 		3.75 		10.75		3.25		19.25		1.5		2.25		8.75 		9.0 		4.25 		4.25																								12/19/2002		Nathan Copeland										9159147.01
T cell receptor expression,  V-gamma-7 positive and V-gamma-4] positive % of total gamma-delta intestinal intraepithelial lymphocytes [%]		Most of the gd T cells in the intestinal epithelium of normal mice use the Vg1 or the Vg7 gene segments. However, the relative proportions of  gd intraepithelial lymphocytes expressing either the Vg1 or the Vg7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gd T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vg1, Vg4, Vg7, and Vd4 to examine the TCR repertoire of intraepithelial gd lymphocytes in a set of (C57BL/6Ę´ĘDBA/2) recombinant inbred strains. Our results show that the representation of different Vg and Vd gene products among gd   intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRg, TCRd, and major histocompatibility complex loci. 	Pereira P, Lafaille JJ, Gerber D, and Tonegawa S	The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility 	Proc Natl Acad Sci USA	94(11)	5761-5766	May	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9159147&dopt=Abstract	9159147		02	2-6 months	60 	180	MF	2	% 					26.5 		6.0 		13.0		5.0 		7.5		9.0 		9.0 		8.5		13.0 		3.5 		8.5 		9.5 		7.5 		9.0 				12.0 		22.5		20.5		19.5 		15.0 		16.5 		30.5		6.0 		21.5 		7.5 		8.5 																								12/19/2002		Nathan Copeland										9159147.02
T cell receptor expression,  V-gamma-7 positive, Vgamma-4 negative, % of total gamma-delta intestinal intraepithelial lymphocytes [%]		Most of the gd T cells in the intestinal epithelium of normal mice use the Vg1 or the Vg7 gene segments. However, the relative proportions of  gd intraepithelial lymphocytes expressing either the Vg1 or the Vg7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gd T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vg1, Vg4, Vg7, and Vd4 to examine the TCR repertoire of intraepithelial gd lymphocytes in a set of (C57BL/6Ę´ĘDBA/2) recombinant inbred strains. Our results show that the representation of different Vg and Vd gene products among gd   intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRg, TCRd, and major histocompatibility complex loci. 	Pereira P, Lafaille JJ, Gerber D, and Tonegawa S	The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility 	Proc Natl Acad Sci USA	94(11)	5761-5766	May	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9159147&dopt=Abstract	9159147		03	2-6 months	60 	180	MF	2	% 					24.0		49.5		21.0		17.5 		57.0 		27.5 		36.5 		27.5 		43.0		38.0 		52.5		34.0 		26.0		58.5				22.0 		26.0 		41.0 		34.0		24.0 		29.5 		31.5		43.0 		27.5 		31.5 		22.5 																								12/19/2002		Nathan Copeland										9159147.03
T cell receptor expression,  V-gamma-1 positive, V-gamma-4 negative, % of total gamma-delta intestinal intraepithelial lymphocytes [%]		Most of the gd T cells in the intestinal epithelium of normal mice use the Vg1 or the Vg7 gene segments. However, the relative proportions of  gd intraepithelial lymphocytes expressing either the Vg1 or the Vg7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gd T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vg1, Vg4, Vg7, and Vd4 to examine the TCR repertoire of intraepithelial gd lymphocytes in a set of (C57BL/6Ę´ĘDBA/2) recombinant inbred strains. Our results show that the representation of different Vg and Vd gene products among gd   intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRg, TCRd, and major histocompatibility complex loci. 	Pereira P, Lafaille JJ, Gerber D, and Tonegawa S	The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility 	Proc Natl Acad Sci USA	94(11)	5761-5766	May	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9159147&dopt=Abstract	9159147		04	2-6 months	60 	180	MF	2	% 					36.5 		34.5		55.5		67.5		39.0		55.5 		49.0		49.0		31.0		41.5 		33.5 		61.5 		51.0		33.5				57.5 		41.5 		35.5		34.0		35.5		44.0 		40.0 		32.0 		36.5 		51.0 		54.5 																								12/19/2002		Nathan Copeland										9159147.04
T cell receptor expression,  V-gamma-7 positive, gamma-4 negative cells, % of total gamma-delta intestinal intraepithelial lymphocytes [%]		Most of the gd T cells in the intestinal epithelium of normal mice use the Vg1 or the Vg7 gene segments. However, the relative proportions of  gd intraepithelial lymphocytes expressing either the Vg1 or the Vg7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gd T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vg1, Vg4, Vg7, and Vd4 to examine the TCR repertoire of intraepithelial gd lymphocytes in a set of (C57BL/6Ę´ĘDBA/2) recombinant inbred strains. Our results show that the representation of different Vg and Vd gene products among gd   intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRg, TCRd, and major histocompatibility complex loci. 	Pereira P, Lafaille JJ, Gerber D, and Tonegawa S	The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility 	Proc Natl Acad Sci USA	94(11)	5761-5766	May	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9159147&dopt=Abstract	9159147		05	2-6 months	60 	180	MF	2	%					27.0		49.5		21.5		17.5				27.0		36.5		27.0		43.0		38.0				34.5		25.5						23.0		26.0		41.0		34.0		24.0		30.0		30.5		45.5		23.5		31.5		22.5																								12/19/2002		Nathan Copeland										9159147.05
Olfactory bulb weight, mg [raw average from strainDB 6/28/00]		Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.	Williams RW, Airey DC, Kulkarni A, Zhou G, Lu L	Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size.	Behav Genet	31(1)	61-77	Jan	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11529276&dopt=Abstract	11529276		01	80 days	80		MF	349 males and 321 females	mg					20.9		23.1		22.3		21.2		20.2		22.0		17.7		20.3		18.0		18.7		18.8		21.5		21.1		18.7		18.2		18.9		21.0				16.9		17.6		17.9		19.1		19.1		17.8		20.4		21.7		20.3		23.0		24.0		17.5		23.0		22.4		19.5		22.0				20.9				6/12/2003	MK Sullivan											11529276.01
Olfactory Bulb Weight, adjusted [mg]		Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.	Williams RW, Airey DC, Kulkarni A, Zhou G, Lu L.	Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size.	Behav Genet	31(1)	61-77	Jan	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11529276&dopt=Abstract	11529276		02	80 days	80		MF	349 males and 321 females	mg	21.9	0.4	21.6	0.3	20.7	0.2	21.1	0.7	18.3	0.5	22.0	0.4	19.3	0.2	20.0	0.4	18.7	0.4	20.0	0.5	19.4	0.2	19.9	0.5	18.0	0.5	19.7	0.4	21.0	0.4	18.6	0.6	20.9	0.5	17.3	0.5	19.8	0.7	18.7	0.5	18.6	0.7	18.3	0.5	20.3	0.3	19.7	0.4	20.1	0.6	20.7	0.6	21.4	0.6	20.1	0.3	20.3	0.4	23.2	0.4	23.6	1.0	18.1	0.5	21.2	2.0	22.5	0.7	20.4	0.3	20.3	0.7			19.3	0.1			6/12/2003	MK Sullivan											11529276.02
Olfactory Bulb Weight CV%		Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.	Williams RW, Airey DC, Kulkarni A, Zhou G, Lu L.	Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size.	Behav Genet	31(1)	61-77	Jan	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11529276&dopt=Abstract	11529276		03	80 days	80		MF	349 males and 321 females	%	4.8		4.4		1.4		3.5		4.2		3.0		3.2		3.5		2.3		2.1		2.9		3.5		2.3		4.7		3.3		4.2		3.4		4.7		3.3		4.2		1.1		3.0		2.5		3.4		2.7		3.6		3.7		4.6		1.8		2.6		1.3		1.3		1.7		3.4		0.4		2.4				2.0				6/12/2003	MK Sullivan											11529276.03
Olfactory Bulb Weight, unadjusted [mg]		Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.	Williams RW, Airey DC, Kulkarni A, Zhou G, Lu L.	Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size.	Behav Genet	31(1)	61-77	Jan	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11529276&dopt=Abstract	11529276		04	80 days	80		MF	349 males and 321 females	mg	22.7		19.8		21.6		21.2		21.2		20.3		22.6		21.7		18.6		20.4		18.5		20.9		19.0		21.7		22.2		18.6		18.8		17.9		20.8		18.1		17.3		17.4		17.7		19.2		19.1		18.6		21.0		19.8		21.0		23.8		24.4		18.2		19.9		23.1		20.4		21.7				21.4				6/12/2003	MK Sullivan											11529276.04
Brain Weight [mg]		Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.	Williams RW, Airey DC, Kulkarni A, Zhou G, Lu L.	Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size.	Behav Genet	31(1)	61-77	Jan	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11529276&dopt=Abstract	11529276		05	80 days	80		MF	349 males and 321 females	mg	495		415		456		440		502		391		498		469		420		447		402		439		449		467		445		432		382		442		444		420		394		410		375		413		403		382		415		432		445		439		449		427		428		437		423		464				469				6/12/2003	MK Sullivan											11529276.05
Body Weight [g]		Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.	Williams RW, Airey DC, Kulkarni A, Zhou G, Lu L.	Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes modulate bulb size.	Behav Genet	31(1)	61-77	Jan	2001		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11529276&dopt=Abstract	11529276		06	80 days	80		MF	349 males and 321 females	g	24.7		19.3		18.8		28.9		22.2		19.9		22.9		23.6		18.8		21.2		19.5		21.7		24.3		23.9		21.3		21.2		19.0		21.8		20.3		20.0		20.7		19.2		20.2		23.1		22.3		18.2		20.8		26.0		17.7		21.1		25.8		17.2		22.5		19.4		20.2		20.2				21.0				6/12/2003	MK Sullivan											11529276.06
Open-field activity following saline injection [number of crossings during 3 min]		Recombinant inbred (RI) strains are valuable not only for detecting major gene segregation and linkage but also for identifying associations between behavior and quantitative trait loci (QTL) that account for relatively small amounts of variation in behaviors for which strain distribution patterns are not bimodal. When applied to published data on genetic markers and on behavior for BXD RI strains, the RI QTL association approach suggests the presence of QTLs on chromosomes 6 and 12 for open-field activity and on chromosomes 1, 2, and 17 for high-pressure seizure susceptibility. Because the RI QTL approach does not require that the progenitor inbred strains of a particular RI series differ, researchers could focus on the BXD RI series, for which the greatest number of genetic markers are available. Focusing on BXD would capitalize on the cumulative nature of RI research which permits analyses of QTL sources of genetic correlations across studies.	Plomin R, McClearn GE,ĘGora-Maslak G,Ę Neiderhiser JM.	Use of recombinant inbred strains to detect quantitative trait loci associated with behavior.	Behav Genet	277(2)	99-116	Mar	1991		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2049054&dopt=Abstract	2049054	91264768	02	100 days	100				number of crossings during 3 min	160		140		180		180		190		160		120				80		140		120		160		100		160		140		160				180				160		120				140		80		180		100																												7/14/2003	MK Sullivan											2049054.02
Plasma corticosterone levels 6 hr post 4 g/kg Ethanol [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	05	65-115 days	65	115	Male	5-15	µg/dl	7	1.03	10.5	1.43	7.5	2.65			10	1.34	10	1.61	6	1.97	12	2.92	3.5	.94	10.5	1.38			7.5	1.20	8	1.35	7.5	1.49	7.5	.67	5	.83			6	1.25					10.5	2.36	3	1.03	4.5	1.68	7.5	1.22	10	.75	7.5	3.07	4	.83	4	1.60																							12/26/2002												8748968.05
Plasma corticosterone levels 6 hr post saline [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav  Neurosci	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	06	65-115 days	65	115	Male	3-9	µg/dl	1	1.22	7.5	0.86	1	1.58			6	.71	2.5	.71	2	.39	3.5	0.00	3	1.07	2	1.06			5.5	1.05	4.5	0.83	3.5	1.30	6	.977	2	0.80			2.5	1.16					3.5	1.79	2.5	1.00	4	1.00	3	1.04	1.5	1.14	5	0.91	4	1.07	4.5	0.98																							12/26/2002												8748968.06
Plasma corticosterone levels 7 hr post 4 g/kg  Ethanol [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	07	65-115 days	65	115	Male	5-15	µg/dl	7	1.37	12	1.90	4	1.45	10	2.07	12	3.68	12.5	2.35	5	1.04	13	2.87	10	2.10	9.5	2.40	6	0.63	6	1.08	9	2.06	7	1.04	5.5	0.77	4	1.42			8	0.87	9.5	2.99			15	3.42			24.5	4.72	8	1.58	15.5	1.69	16	2.00	8.5	3.16	13	2.10																							12/26/2002												8748968.07
Handling-induced convulsion scores 7 hr post 4 g/kg Ethanol		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	08	65-115 days	65	115	Male	5-15		0.2	0.19	3	0.19	0.8	0.29	2.4	0.75	0.9	0.15	0	0	0.9	0.23	2	0.25	0.7	0.15	0.4	0.20	1.8	0.37	1.4	0.28	0.9	0.08	0.4	0.22	0.3	0.14	0	0			0.9	0.27	0.8	0.15			0	0			1.2	0.18	0.8	0.16	0.1	0.07	2.3	0.21	0	0	1.8	0.41																							12/26/2002												8748968.08
Preconditioned stimulus [% freezing]		Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task.	Owen EH, Christensen SC, Paylor R, Wehner JM	Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.	Behav Neurosci 	111(2)	292-300	Apr	1997		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9106670&dopt=Abstract	9106670	97260550	03	60-134 days 	60	134	MF	9-20	% freezing	32	0.423	10	0.200	5	1.69	11	2.31			5	1.38	30	12.00	15	3.23	22	5.00	7	2.00	20	4.46	6	2.00			17	2.58			6	2.08			27	6.62	35	4.62	35	6.77	15	3.46	10	3.34	32	3.62	32	4.31	0	0.00	5	1.69			40	5.31																							6/12/2003	MK Sullivan											9106670.03
Floor preference test - average time on grid floor (control group) [s/min]	table 2 col 4	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	14	56-125 days	56	125	Male	6-16	s/min	29.6	2.4	33.4	2.7	31.3	3.1	35.2	3.5	26.9	2.6	33.7	3.1	28.6	2.3	32.4	2.0	30.7	2.7	26.5	3.1	24.7	1.8	29.7	1.8	25.6	1.6	27.3	3.6	31.3	1.3					28.8	1.5	23.2	3.4			38.0	3.2	31.5	2.3	31.6	4.0	32.1	3.2	31.5	1.4																													6/23/2003	MK Sullivan											7480533.14
Floor preference test, average time on grid textured floor (control group) [s/min]	table 2 col 5	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	16	56-125 days	56	125	Male	6-16	s/min	41.5	3.8	40.2	1.8	29.4	2.4	30.1	3.5	29.3	1.6	31.4	2.9	33.4	1.3	43.8	3.2	29.0	1.5	40.0	4.2	30.6	2.2	40.7	2.9	29.5	1.7	24.1	1.6	48.0	2.7					37.9	1.8	26.6	2.3			20.9	2.4	34.8	2.4	38.3	4.5	31.7	2.1	66.8	5.7																													6/23/2003	MK Sullivan											7480533.16
Floor preference test - preference for grid textured floor in Conditioned Place Preference Apparatus (experimental group)[activity/min]	table 3 col 3	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	06	56-125 days	56	125	Male	7-17	activity/min	38.5	2.5	42.8	2.4	31.0	1.9	37.8	2.5	27.9	0.9	31.4	1.4	33.5	1.8	47.3	1.9	25.8	1.7	37.1	2.9	26.8	1.9	40.2	2.5	30.1	1.5	21.2	1.4	52.2	2.3					39.9	1.7	26	1.4			22.9	1.3	36.2	2.1	42.3	2.8	32.7	2.2	88.7	4.1																													6/23/2003	MK Sullivan											7480533.06
Granulocyte Colony Stimulating Factor induced   Progenitor cell mobilization from bone marrow to blood [PB-CFC/µl]		Granulocyte colony-stimulating factor (G-CSF) can effectively mobilize hematopoietic stem and progenitor cells from bone marrow into blood, thereby allowing peripheral blood stem cells (PBSCs) to be used for transplantation. The efficiency of PBSC mobilization response to G-CSF is a multigene trait. DBA/2 (high-responder) and C57BL/6 (low-responder) mice were used for a genetic analysis of G-CSF-induced progenitor release. Significant linkages were found on chromosome 2Ęby analyzing segregation distortion among the high responders of 500Ębackcross mice and on chromosome 11Ęby using the quantitative trait locus analysis of 26Ęstrains of BXD recombinant inbred mice. 	Hasegawa M,  Baldwin TM, Metcalf D, Foote SJ	Progenitor cell mobilization by granulocyte colony-stimulating factor controlled by loci on chromosomes 2 and 11.	Blood 	95(5)	1872-1874	Mar	2000		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10688851&dopt=Abstract	10688851		01	7-11 wks	49	77	MF	2-3	PB-CFC/µl					0.6		0.5		0.5		1.0		0.6		6.8		0.7		0.6		0.9		3.6		2.1		4.0		2.0		1.4		3.1		1.2		1.0		6.7		5.2		1.4		2.5		1.6		2.8		1.0		2.2																										7/7/2003	MK Sullivan	Nathan Copeland										10688851.01
Retinal area [mm2]		PURPOSE: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped. METHODS: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J. RESULTS: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2. CONCLUSIONS: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.	Zhou G, Williams RW	Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse.	Invest Ophthalmol Vis Sci	40(5)	817-825	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102277&dopt=Abstract	10102277	99200400	05	106 days	106		MF	8-35	mm^2	18.5		20.1		19.8		20.2		19.1		19.8		18.6		19.3		20.2		18.9		19.3		18.7		19.3		19		18.1		19.7		18.8		16.2		19.5		18.2		17		17.6		18.9		17.8		19.3		18.4		19.2		19.3																								6/12/2003	MK Sullivan											10102277.05
Retinal ganglion cell number [cells x1000]		Common genetic polymorphisms-as opposed to rare mutations-generate almost all heritable differences in the size and structure of the CNS. Surprisingly, these normal variants have not previously been mapped or cloned in any vertebrate species. In a recent paper (), we suggested that much of the variation in retinal ganglion cell number in mice, and the striking bimodality of strain averages, are caused by one or two quantitative trait loci (QTLs). To test this idea, and to map genes linked to this variable and highly heritable quantitative trait, we have counted ganglion cells in 38 recombinant inbred strains (BXD and BXH) derived from parental strains that have high and low cell numbers. A genome-wide search using simple and composite interval-mapping techniques revealed a major QTL on chromosome (Chr) 11 in a 3 cM interval between Hoxb and Krt1 (LOD = 6.8; genome-wide p = 0.001) and possible subsidiary QTLs on Chr 2 and Chr 8. The Chr 11 locus, neuron number control 1 (Nnc1), accounts for one third of the genetic variance among BXH strains and more than half of that among BXD strains, but Nnc1 has no known effects on brain weight, eye weight, or total retinal cell number. Three strong candidate genes have been mapped previously to the same region as Nnc1. These genes-Rara, Thra, and Erbb2- encode receptors for retinoic acid, thyroxine, and neuregulin, respectively. Each receptor is expressed in the retina during development, and their ligands affect the proliferation or survival of retinal cells.	Williams RW, Strom RC., Goldowitz D	Natural variation in neuron number in mice is linked to a major quantitative trait locus on Chr 11.	J Neurosci	18(1)	138-46	Jan	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9412494&dopt=Abstract	9412494	98075112	02	100 days	100		MF	5-11	cells x1000	55.4	0.8	63.4	1.2	60.3	1.1	65.9	1.8	75.5	1.3	62.7	0.9	62.8	2.1	65.6	1.7	61	1.1	56.8	2.1	54.7	1.7	64	1.6	63.8	1.1	64	1.3	55.1	0.9	67.1	1.3	59.9	1.9	60	1.5	64.5	1.1	53	1.0	62.4	1.0	53.8	1.5	50.8	1.1	52.4	1.9	63.6	1.4	66	1.3	66.6	1.2	75.8	2.2																							6/18/2003	MK Sullivan											9412494.02
Retinal ganglion cell number (x1000)		PURPOSE: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped. METHODS: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J. RESULTS: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2. CONCLUSIONS: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.	Zhou G, Williams RW	Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse.	Invest Ophthalmol Vis Sci	40(5)	817-825	Apr	1999		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102277&dopt=Abstract	10102277	99200400	06	106 days	106		MF	8-35	x1000	55.4		63.4		60.3		65.9		75.5		62.7		62.8		65.6		61		56.8		54.7		64		63.8		64		55.1		67.1		59.9		60		64.5		53		62.4		53.8		50.8		52.4		63.6		66		66.6		75.8																								6/12/2003	MK Sullivan											10102277.06
Saccharin intakes post-saline, pre-exposed to saccharin, group 0 g/kg and trial 1 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	01	56-125 days	56	125	Male	5-12	ml	3.44	0.15	2.47	0.19	3.14	0.21	3.35	0.25	3.2	0.14	2.87	0.08	2.36	0.12	3.33	0.22	3.26	0.17	2.69	0.23	3.1	0.11	3.85	0.14	3.84	0.22	3.32 	0.20	3.79	0.29					3	0.43					2.71	0.21 	3.09	0.13	2.75	0.17	2.56	0.20	3.57	0.26					3.55	0.26																							12/26/2002			SACSsaccharin									9756038.01
Saccharin intakes post-saline, pre-exposed to saccharin, group 0 g/kg and trials 2-4 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	02	56-125 days	56	125	Male	5-12	ml	3.15	0.15	2.77	0.15	2.84	0.23	3.74	0.36	3.25	0.21	2.88	0.09	2.41	0.13	3.46	0.21	3.09	0.08	2.54	0.18	2.87	0.11	3.75	0.08	3.93	0.12	3.02	0.13	3.66	0.23					3.08	0.48					2.6	0.16	2.47	0.12	2.63	0.17	2.73	0.15	3.2	0.19					3.7	0.25																							12/26/2002			SACSsaccharin									9756038.02
Ethanol induced conditioned taste aversion to saccharin, group 2 g/kg and trial 1 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	03	56-125 days	56	125	Male	4-20	ml	3.22	0.22	3.01	0.13	3.13	0.19	3.75	0.31	3.4	0.21	2.79	0.10	2.71	0.20	3.03	0.20	3.45	0.21	2.88	0.23	3.63	0.24	3.85	0.26	3.71	0.18	2.72	0.15	3.67	0.20					3.03	0.26					2.69	0.14	3.03	0.15	2.69	0.14	2.81	0.19	3.2	0.19					3.26	0.21																							12/26/2002			SACSsaccharin									9756038.03
Ethanol induced conditioned taste aversion to saccharin, group 2 g/kg and trial 2-4 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	04	56-125 days	56	125	Male	4-20	ml	2.99	0.12	2.83	0.11	2.87	0.19	3.44	0.46	2.24	0.27	2.49	0.11	2.75	0.20	2.69	0.28	2.73	0.13	2.55	0.13	3.34	0.25	3.16	0.19	3.47	0.14	2.82	0.14	3.24	0.24					2.8	0.19					2.32	0.17	2.14	0.12	2.62	0.12	2.55	0.22	3.08	0.11					3.04	0.12																							12/26/2002			SACSsaccharin									9756038.04
Ethanol induced conditioned taste aversion to saccharin, group 4 g/kg and trial 1 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	05	56-125 days	56	125	Male	5-17	ml	3.49	0.13	2.79	0.15	2.87	0.21	3.84	0.39	3.8	0.15	2.94	0.16	2.44	0.17	3.36	0.25	3.26	0.04	2.79	0.18	3.68	0.27	4.41	0.13	3.56	0.21	3.02	0.15	3.47	0.23					3.22	0.29					3.03	0.25	2.99	0.12	2.62	0.12	2.66	0.19	3.39	0.15					3.21	0.13																							12/26/2002			SACSsaccharin									9756038.05
Ethanol induced conditioned taste aversion to saccharin, group 4 g/kg and trials 2-4 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	06	56-125 day s	56	125	Male	5-17	ml	2.64	0.06	1.66	0.12	2.39	0.17	2.8	0.28	1.59	0.16	2.28	0.14	2.28	0.10	2.22	0.36	2.37	0.10	2.18	0.15	2.28	0.23	2.78	0.21	2.39	0.16	2.78	0.14	2.88	0.23					2.37	0.21					1.9	0.20	1.8	0.07	2.26	0.17	2.18	0.19	2.14	0.21					2.00	0.18																							12/26/2002			SACSsaccharin									9756038.06
Saccharin intake post EtOH no saccharin pre-exposure group UP and trial 1 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.	Risinger FO, Cunningham CL	Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice	Alcohol Clin Exp Res	22(6)	1234-1244	Sept	1998		http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9756038&dopt=Abstract	9756038	98427469	07	56-125 days	56	125	Male	4-12	ml	2.93	0.09	3.2	0.17	2.8	0.20	3.3	0.15	3.41	0.14	2.77	0.11	2.74	0.23	3.16	0.18	2.83	0.16	3.2	0.23	3.1	0.23	3.47	0.30	3.79	0.16	3.16	0.20	2.94	0.20					2.61	0.20					2.58	0.18	3.12	0.18	2.74	0.22	2.41	0.17	3.33	0.18					3.49	0.20																							12/26/2002			SACSsaccharin									9756038.07
Saccharin intake post EtOH no saccharin pre-exposure group UP and trials 2-4 [ml]		Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (et