Purpose: A mouse mutant expressing a bilateral nuclear and radial cataract was found after paternal treatment with chlorambucil. The purpose of this study was to establish the linkage of the mutation to a particular chromosome to allow molecular characterization. Moreover, the mutants were examined morphologically.
Methods: Isolated lenses were photographed and histologic sections of the eye were analyzed according to standard procedures. The mutation was localized to chromosome 1 by allelism testing with the Cryge(nz) mutation. Candidate genes were amplified by PCR from cDNA or genomic DNA and sequenced.
Results: A novel mouse cataract was characterized by a nuclear and radial opacification of the lens. The lenses of the mutants are smaller than those of the wild type. The histologic analysis demonstrated degeneration of lens fibers in the lens core. Abnormal remnants of cell nuclei are present throughout the entire lens. Genetic analysis revealed allelism to the Cat2 group of dominant cataracts on mouse chromosome 1; therefore, the cluster of the Cryg genes and the closely linked Cryba2 gene were tested as candidates. A 6-bp deletion in exon 3 of the gammaC-crystallin encoding gene (Crygc) is causative for the cataract phenotype; the mutation is therefore designated CrygcChl3. The deletion of the bases 420 to 425 leads to a loss of two amino acids, Gly and Arg, in the fourth Greek-key motif.
Conclusions: The CrygcChl3 is the first mutation in the mouse affecting the Crygc gene. Dominant mutations for five of the six Cryg genes on mouse chromosome 1 have now been characterized, demonstrating the importance of this gene cluster for lens transparency.