title: A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain.
abstract: A substrain of mice originating from the CF#1 strain (an outbred colony) reared at Osaka Prefecture University (CF#1/lr mice) develops cataracts beginning at 4 weeks of age. Affected mice were fully viable and fertile and developed cataracts by 14 weeks of age. Histologically, CF#1/lr mice showed vacuolation of the lens cortex, swollen lens fibers, lens rupture and nuclear extrusion. To elucidate the mode of inheritance, we analyzed heterozygous mutant hybrids generated from CF#1/lr mice and wild-type BALB/c mice. None of the heterozygous mutants were affected, and the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. For the initial genome-wide screening and further mapping, we used affected progeny of CF#1/lr × (CF#1/lr × BALB/c) mice. We concluded that the cataracts in CF#1/lr mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 3 between D3Mit79 and D3Mit216. In this region, we identified 8 genes associated with ocular disease. All 8 genes were sequenced and a novel point mutation (1 bp insertion of cytosine) in exon 7 of the Bcar3 gene was identified. This mutation produced a premature stop codon and a truncated protein. In conclusion, we have identified the first spontaneous mutation in the Bcar3 gene associated with lens extrusion cataracts. This novel cataract model may provide further knowledge of the molecular biology of cataractogenesis and the function of the BCAR3 protein.
authors.affiliation: Department of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, 1-58 Rinku Ourai kita, Izumisano, Osaka, 598-8531, Japan. kondo@vet.osakafu-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, 1-58 Rinku Ourai kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Nakamori
authors.affiliation: Department of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, 1-58 Rinku Ourai kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Department of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, 1-58 Rinku Ourai kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Takeshita
authors.affiliation: Laboratory of Basic Veterinary Science, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, 753-8515, Japan.
authors.forename: Ken-Takeshi
authors.initials: KT
authors.lastname: Kusakabe
authors.affiliation: Department of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, 1-58 Rinku Ourai kita, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Okada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D007908:Lens, Crystalline / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D017354:Point Mutation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C120867:Bcar3 protein, mouse; D020662:Guanine Nucleotide Exchange Factors