International Mammalian Genome Society

E57 Physical Mapping in the psr Region of Mouse Chromosome 7

Lisa S. Webb¹, Madhu S. Dhar¹, and Dabney K. Johnson^1,2. ¹The University of Tennessee Graduate School of Biomedical Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6480, USA; ²Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-8077

We have identified two independently generated, ENU-induced recessive mutations, 723SJ and 1060SJ, that cause a neurological phenotype we call psr, for profound seizures and runting. Both mutations are closely-linked to the mouse pink-eyed dilution (p) locus in Chromosome 7. Animals homozygous or hemizygous for these mutations are runted, develop severe and nearly continual seizures, and die between 15 and 18 days postnatal. These non-complementing mutations have indistinguishable phenotypes, map to the same interval in the p-region deletion complex, and are assumed to be allelic.

As a first step in positionally cloning the gene responsible for the psr phenotype, we are building a sequence-ready contig of genomic clones covering the minimal interval determined to contain the gene. A mouse BAC library was screened by PCR using primers for the microsatellite markers previously determined to map in the region. Terminal sequences of these BACs and internal sequences generated by single-primer PCR were subcloned, and these probes were used to check for overlap and align the contig. Sequencing of these BACs is in progress; candidate genes will be evaluated for altered RNA expression in the two mutant alleles and verified by DNA resequencing.