Further genetic analysis of two autosomal dominant mouse eye defects, Ccw and Pax6(coop)

PURPOSE: The work forms part of a major project to study the genetics of mo use cataract mutants found during the course of mutagenesis experiments. Th e long-term aim is to find the underlying gene mutation in each cataract mu tant. Here we report further studies of the mutant cataract and curly whisk ers (Ccw), previously mapped to Chromosome 4, and also investigations of th e corneal opacity (Coop) mutant, which is shown to involve a mutation in th e Pax6 gene. METHODS: For Ccw, the methods included mapping relative to microsatellite m arkers and histological studies. For the Coop mutant, breeding methods were used to show that Coop was allelic with Pax6. The Pax6 coding region in th e mutant was then sequenced. RESULTS: The Ccw locus was mapped to approximately position 45cM on the con sensus map of Chr 4. Histologically, progressive degeneration of the lens w as seen. In the Coop mutant, a base-pair change C->T was found at position 1033 in the Pax6 gene, which created a stop codon leading to premature term ination of translation, and to a truncated Pax6 protein. CONCLUSIONS: The phenotype in Ccw/+ heterozygotes involves a new type of le ns degeneration in the mouse. On the basis of the phenotype and the locus p osition, no candidate gene has yet been identified. The Pax6(coop) mutant d iffers in phenotype from known null alleles of Pax6, implying that it is a hypomorph.