A deletion in a element of causes cataracts and microphthalmia in mice

The Rinshoken cataract () mutation, which causes congenital cataracts, is a recessive mutation found in SJL/J mice. All mutants present with opacity in the lens by 2 months of age. The locus was mapped to a 1.6-Mb region in Chr 4 that contains the gene. This gene is responsible for cataracts in humans and mice, and it plays a crucial role in the development of the lens. Furthermore, mutation of causes various ocular defects. We sequenced the genomic region of , including the coding exons and UTRs; however, no mutations were discovered in these regions. Because there were no differences in sequences between the / and wild-type mice, we inferred that a mutation was located in the regulatory regions of the gene. To test this possibility, we sequenced a 5′ noncoding region that is highly conserved among vertebrates and is predicted to be the major enhancer of . This analysis revealed a deletion of 22-bp located approximately 3.2-kb upstream of the start codon of in mice. Moreover, we demonstrated by RT-PCR and in situ hybridization that the mutant has reduced expression of in the lens during development. We therefore suggest that cataracts in mice are caused by reduced expression in the lens and that this decreased expression is a result of a deletion in a -acting regulatory element.