International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F29 Mutation in the cbA3/A1-Crystallin Encoding Gene Cryba1 Causes a Dominant Cataract in the Mouse

J. Graw, J. Löster, A. Reis*, E. Wolf#, R. Balling, M. Hrabé de Angelis. GSF-Research Center for Environment and Health, Institute of Mammalian Genetics, D-85764 Neuherberg, Germany; *Max-Delbrück-Center for Molecular Medicine, Institute of Molecular Genetics, D-13122 Berlin, Germany; #Lehrstuhl für Molekulare Tierzucht und Haustiergenetik, Ludwig-Maximilians-Universität München, D-81375 München, Germany

During the Munich 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 foetal nucleus, which progresses and form a nuclear opacity. Since the homozygotes have the cataract already developed at eye opening, the mode of inheritance is semi-dominant.

Linkage analysis was performed using a set of genome-wide microsatellite markers. The mutation was mapped on 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 bA3/A1-crystallin encoding gene Cryba1 an excellent candidate gene.

The mouse Cryba1 was amplified from lens mRNA by RT-PCR. Sequence analysis revealed a mutation of a T to an A at the second base of exon 6 predicting an exchange of Trp by Arg. Moreover, this exchange creates also an alternative splice site, which is used in about 30% of the mRNA. It leads to an intron which is 3 bp longer predicting the loss of the Trp residue. Computer analysis suggests that in the case of Trp/Arg exhange the 4th Greek key motif of the affected bA3/A1-crystallin will not be formed. The mutation will be referred to as Cryba1po1.

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.

 


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