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Jochen Graw, Jana Löster, Dian Soewarto, Helmut Fuchs, Birgit Meyer, André Reis, Eckhard Wolf, Rudi Balling, Martin Hrabé de Angelis; Characterization of a New, Dominant V124E Mutation in the Mouse αA-Crystallin–Encoding Gene. Invest. Ophthalmol. Vis. Sci. 2001;42(12):2909-2915.
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purpose. During an ethylnitrosourea (ENU) mutagenesis screening, mice were
tested for the occurrence of dominant cataracts. The purpose of the
study was morphologic description, mapping of the mutant gene, and
characterization of the underlying molecular lesion in a particular
methods. Isolated lenses were photographed and histologic sections of the eye
were analyzed according to standard procedures. Linkage analysis was
performed with a set of microsatellite markers covering all autosomal
chromosomes. cDNA was amplified after reverse transcription of lens
mRNA. For PCR, cDNA or genomic DNA was used as a template.
results. Nuclear opacity and posterior suture anomaly were visible at eye
opening and progressed to a nuclear and zonular cataract at 2 months of
age. The opacity as well as the microphthalmia was more pronounced in
the homozygotes than in the heterozygotes. The mutation was mapped to
chromosome 17 between the markers D17Mit133 and D17Mit180. This position made theα
A-crystallin–encoding gene (Cryaa) an excellent
candidate gene. Sequence analysis revealed a mutation of a T to an A at
position 371 in the Cryaa cDNA. The mutation was
confirmed by an additional MnlI restriction site in the
genomic DNA of homozygous mutants leading to replacement of Val with
Glu at codon 124 affecting the C-terminal region of theα
conclusions. The Aey7 mutant represents the first dominant mouse
cataract mutation affecting the Cryaa gene. The mutation
leads to progressive opacification of the lens. Compared with the β-
and γ-crystallin–encoding genes, mutations in theα
-crystallin–encoding genes are rare.
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