title: A 1-bp deletion in the gammaC-crystallin leads to dominant cataracts in mice.
abstract: To date around 140 genetic alleles have been identified as being responsible for mouse cataract pathology, including Crya, Cryb, Cryg, Maf, Pax6, Pitx3, Sox, Connexins, MIP, and Lim-2. We obtained a dominant cataract mouse model from a spontaneous mutation in the F1 hybrids of outbred strain ICR mice crossed to the inbred strain BALB/cJ mice. Heterozygous and homozygous mutants expressed a nuclear cataract in both eyes. In 8-day-old mice, histological analysis showed that polygon epithelial cells were in the equatorial region and cortex underneath, and vacuole and sponge-like degeneration were in the cortical area underneath the posterior lens capsule. The nucleus of the lens was a deeply stained pink, with the shorter fibers losing their normal arrangement. For the entire eye, there was a blank zone in the equatorial region in 8-day-old mice; however, there was a certain degree of atrophy in cornea tension and retina in the lens in 3-month-old mice. The lens had been serious damaged in the homozygous mutants. For mutation mapping, heterozygous carriers were mated to wild-type C3H/HeJ mice, and offspring (F1 generation) with cataracts were backcrossed to the wild-type C3H/HeJ mice again. N2 mice with cataracts were used for genotyping. Using genome-wide linkage analysis, the mutation was mapped to chromosome 1 and the Cryg gene cluster between two markers was confirmed as the candidate gene. After direct sequencing the cDNA of the Cryg gene cluster, a 1-bp deletion was found in exon 3 of the Crygc gene, leading to a stop codon at the 76th amino acid of exon 3 which results in production of a truncated protein in mutant mice (Leu160Stop). Bioinformatic analysis of the mutant gammaC-crystallin reveals that the COOH-terminal of the mutant protein deletes a beta-sheet, which affects the function of the lens proteins and leads to the development of cataracts.
authors.affiliation: Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Zhao
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Shimin
authors.initials: S
authors.lastname: Bao
authors.forename: Yuxun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yinming
authors.initials: Y
authors.lastname: Liang
authors.forename: Guoji
authors.initials: G
authors.lastname: Zhao
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Junhua
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch / Q000502:physiology; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D007908:Lens, Crystalline / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000502:physiology; D038222:gamma-Crystallins / Q000235:genetics*
chemical_list: D038222:gamma-Crystallins; C554179:gammaC-crystallin protein, mouse