Project 1: The Mouse Brain Library Project 2: Internet Microscopy (iScope) Project 3: Neurocartographer and Segmentation of the MBL Project 4: The Neurogenetics Tool Box
















Principal Investigator/Program Director Williams, Robert W.


Measuring brain weight.  

A simple analysis of differences in brain weight among numerous strains of mice has been carried out in part as a prelude to this program project. For the great majority of animals, we now have information on sex, body weight, age, and type and quality of fixation. Both sexes and a wide range of ages have been studied and incorporated into the MBL. Perhaps the most remarkable aspect of the data is that they reveal large differences in brain weight between several substrains of mice that carry only modest genetic differences. For instance, brain weights of BALB/cByJ and BALB/cJ mice differ by 76 mg. C57L/J and C57BL/6J differ by 88 mg. C3H/HeJ and C3H/HeSnJ also differ by 88 mg. The closely matched differences in these three pairs are tantalizing. Presumably, the differences are generated by a very small number of polymorphic genesprobably one or two genes. Since some of the parental strains were already fully inbred prior to being split into substrains, it is unlikely that the variation is due to the fixation of alternative alleles. Mutations or reversions are a more likely cause of this remarkable substrain variation. Unfortunately these large differences cannot easily be mapped because suitable polymorphic marker loci for this type of analysis have not yet been developed. However, comparative gene expression analysis (e.g., differential display), subtractive hybridization, and candidate gene approaches might be used to explore factors that contribute to these 80-mg differences.

In a standard mouse colony, variation in brain weight has a heritability that ranges from 0.35 to 0.7 . The correlation between values is a direct estimate of heritability in a narrow sense. Parents and offspring in this case are seven sequential generations (F2 to G10) of an advanced intercross between C57BL/6J and DBA/2J (G. Zhou and R.W. Williams, in progress). This estimate of heritability is somewhat lower than that found in most previous work, averaging 0.35 to 0.45 for different datasets and crosses.

In comparison to brain weight, variation in neuron number has a heritability of approximately 0.8 for granule cells in the dentate gyrus and between 0.7 and 0.9 for retinal ganglion cells . These values are sufficiently high to motivate a QTL analysis.





Selectivity of QTLs