A High-Resolution Genetic Map of the Nervous Locus on Mouse Chromosome 8

The nervous (nr) mutant mouse displays two gross recessive traits: both an exaggeration of juvenile hyperactivity and a pronounced ataxia become apparent during the third and fourth postnatal weeks. Using an intersubspecific intercross, we have established a high-resolution map of a segment of mouse Chromosome 8 that places thenrlocus in a genomic segment defined byD8Rck1on the centromeric end andD8Mit3on the telomeric end. This map position places thenrlocus within the BALB/cGr congenic region of the C3HeB/FeJ-nrstrain, confirming the accuracy of our study. We used this map position to identify and evaluate three genes—ankyrin 1, cortexin, and farnesyltransferase—as candidates for thenrgene. These three genes were eliminated from consideration but allowed us to establish the conservation of synteny between the region containing thenrlocus and a segment of the short arm of human chromosome 8 (8p21–p11.2). Finally, the incomplete penetrance of thenrphenotype led us to perform a screen for modifier loci, and we present evidence that such a nervous modifier locus may exist on mouse Chromosome 5.