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Mutation in the beta A3/A1-crystallin encoding geneCryba1 causes a dominant cataract in the mouse

Item Type:Article
Title:Mutation in the beta A3/A1-crystallin encoding geneCryba1 causes a dominant cataract in the mouse
Creators Name:Graw, J., Jung, M., Loester, J., Klopp, N., Soewarto, D., Fella, C., Fuchs, H., Reis, A., Wolf, E., Balling, R. and de Angelis, M.H.
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.
Keywords:Amino Acid Sequence, Animal Disease Models, Base Sequence, beta-Crystallin A Chain, Cataract, Crystallins, Dominant Genes, Ethylnitrosourea, Genes, Inbred C3H Mice, Inbred C57BL Mice, Messenger RNA, Microsatellite Repeats, Molecular Sequence Data, Mutagenesis, Mutagens, Mutant Strains Mice, Polymerase Chain Reaction, RNA Splicing, Specific Pathogen-Free Organisms, Animals, Mice
Publisher:Academic Press
Page Range:67-73
Date:15 November 1999
Official Publication:https://doi.org/10.1006/geno.1999.5974
PubMed:View item in PubMed

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