title: Mutation in the betaA3/A1-crystallin encoding gene Cryba1 causes a dominant cataract in the mouse.
abstract: During the mouse ENU mutagenesis screen, mice were tested for the occurrence of dominant cataracts. One particular mutant was discovered as a progressive opacity (Po). Heterozygotes show opacification of a superficial layer of the fetal nucleus, which progresses and finally forms a nuclear opacity. Since the homozygotes have already developed the total cataract at eye opening, the mode of inheritance is semidominant. Linkage analysis was performed using a set of genome-wide microsatellite markers. The mutation was mapped to chromosome 11 distal of the marker D11Mit242 (9.3 +/- 4.4 cM) and proximal to D11Mit36 (2.3 +/- 2.3 cM). This position makes the betaA3/A1-crystallin encoding gene Cryba1 an excellent candidate gene. Mouse Cryba1 was amplified from lens mRNA. Sequence analysis revealed a mutation of a T to an A at the second base of exon 6, leading to an exchange of Trp by Arg. Computer analysis predicts that the fourth Greek key motif of the affected betaA3/A1-crystallin will not be formed. Moreover, the mutation leads also to an additional splicing signal, to the skipping of the first 3 bp of exon 6, and finally to the deletion of the Trp residue. Both types of mRNA are present in the homozygous mutant lenses. The mutation will be referred to as Cryba1(po1). This particular mouse mutation provides an excellent animal model for a human congenital zonular cataract with suture opacities, which is caused by a mutation in the homologous gene.
authors.affiliation: Institute of Mammalian Genetics, GSF-Research Center for Environment and Health, Neuherberg, D-85764, Germany. graw@gsf.de
authors.forename: J
authors.initials: J
authors.lastname: Graw
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Löster
authors.forename: N
authors.initials: N
authors.lastname: Klopp
authors.forename: D
authors.initials: D
authors.lastname: Soewarto
authors.forename: C
authors.initials: C
authors.lastname: Fella
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: A
authors.initials: A
authors.lastname: Reis
authors.forename: E
authors.initials: E
authors.lastname: Wolf
authors.forename: R
authors.initials: R
authors.lastname: Balling
authors.forename: M
authors.initials: M
authors.lastname: Hrabé de Angelis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D003459:Crystallins / Q000235:genetics*; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000494:pharmacology; D005260:Female; D005796:Genes; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D038205:beta-Crystallin A Chain
chemical_list: C489108:CRYBA1 protein, human; C051374:Cryba1 protein, mouse; D003459:Crystallins; D009153:Mutagens; D012333:RNA, Messenger; D038205:beta-Crystallin A Chain; D005038:Ethylnitrosourea