A number of murine cataract mutations have been localized to chromosome 1 close to the γ-crystallin gene cluster (Cryg) (Everett et al., 1994, Genomics 20: 429-434; Loster et al., 1994, Genomics 23: 240-242). Based on the size of the mapping or allelism tests they have not been shown to be genetically distinct and have been assigned to locus symbol Cat2. Here we assign three mutations to the respective γ-crystallin gene. Using a systematic candidate gene approach to analyze the entire Cryg cluster, an A→G transition was found in exon 2 of Cryga for the ENU-436 mutation and is designated Cryga(1Neu). The mutant allele Crygb(nop) (formerly Cat2(nop)) is caused by a replacement of 11 bp by 4 bp in the third exon of Crygb, while a C→G transversion in exon 3 of Cryge has been found for the Cryge(t) (formerly Cat2(t)) mutation. For the mutation Cryga(1Neu), an Asp→Gly exchange is deduced, whereas the mutations Crygb(nop) and Cryge(t) lead to the formation of in-frame stop codons and give rise to truncated proteins of 144 and 143 amino acids, respectively. The effects of the mutations upon γ- crystallin structure are likely to be quite different. The Cryga(1Neu) mutation is expected to affect the link between Greek-key motifs 2 and 3, whereas both Crygb(nop) and Cryge(t) mutations are supposed to truncate the fourth Greek-key motif. All three mutations are predicted to alter protein folding of the γ-crystallins and result in lens cataract, but the phenotype for each is quite distinctive.
- Eye lens
- Sequence analysis