Rcn1: A Locus on Mouse Chromosome 11 That Controls Natural Variation in Neuron Number R. W. Williams, R. C. Strom, and D. Goldowitz.

We are interested in genetic and cellular processes that control the size of neuron populations. We performed a quantiative genetic analysis to assess the magnitude of gene control over the retinal ganglion cell population in mouse. Narrow sense heritability, h2, is approximately 0.50. We used BXD recombinant inbred (RI) strains to map quantitative trait loci (QTLs) that contribute to the substantial variation in numbers of retinal ganglion cells. Each BXD strain is a unique, but stable genetic mosaic of C57BL/6 and DBA/2 alleles. An average of 6 cases per strain were phenotyped to determine the mean population associated with each genotype. Optic nerves of over 158 cases were analyzed using a uniform quantitative electron microscopic protocol. The maternal strain (C57BL) has 53,900 ± 1,400 cells, while the paternal strain (DBA) has 62,400 ± 1,100. BXD strain averages range from 50,000 in BXD23 to 78,000 in BXD32. The distribution of strain averages is approximately bimodal (8 strains with a mode close to 55,000; 15 strains with a mode close to 65,000, the average SEM is ± 1,800). The program Map Manager QTL v2.6a was used to test for correlation between this quantitative trait and alleles at more than 1,000 loci mapped on BXD strains. The tightest linkage was to a micro-satellite locus (D11Mit14) mapped distal to Hoxb in the AntP91a gene on chromosome 11 (F=24.96; p=.000094; lod ~4.0, 2 recombinants of 20 mutually typed strains). Allelic variants at the retinal QTL, which we are provisionally calling retinal cell number 1 (Rcn1), probably account for a difference of about 4,000 ganglion cells between strains.