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

ABSTRACT

PURPOSE: The work forms part of a major project to study the genetics of mouse cataract mutants found during the course of mutagenesis experiments. The long-term aim is to find the underlying gene mutation in each cataract mutant. Here we report further studies of the mutant cataract and curly whiskers (Ccw), previously mapped to Chromosome 4, and also investigations of the corneal opacity (Coop) mutant, which is shown to involve a mutation in the Pax6 gene. METHODS: For Ccw, the methods included mapping relative to microsatellite markers and histological studies. For the Coop mutant, breeding methods were used to show that Coop was allelic with Pax6. The Pax6 coding region in the mutant was then sequenced. RESULTS: The Ccw locus was mapped to approximately position 45cM on the consensus map of Chr 4. Histologically, progressive degeneration of the lens was 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 termination of translation, and to a truncated Pax6 protein. CONCLUSIONS: The phenotype in Ccw/+ heterozygotes involves a new type of lens degeneration in the mouse. On the basis of the phenotype and the locus position, no candidate gene has yet been identified. The Pax6coop mutant differs in phenotype from known null alleles of Pax6, implying that it is a hypomorph.