Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy

摘要: Expansion of a CTG trinucleotide repeat in the 3′ UTR gene DMPK at DM1 locus on chromosome 19 causes myotonic dystrophy1,2,3, dominantly inherited disease characterized by skeletal muscle dystrophy and myotonia, cataracts cardiac conduction defects. Targeted deletion Dm15, mouse orthologue human DMPK, produced mice with mild myopathy4,5 abnormalities6, but without other features dystrophy, such as myotonia cataracts. We, others, have demonstrated that expansion decreases expression adjacent SIX5 (refs 7,8), which encodes homeodomain transcription factor. To determine whether deficiency contributes to phenotype, we disrupted Six5 replacing first exon β-galactosidase reporter. Six5-mutant showed reporter multiple tissues, including developing lens. Homozygous mutant had no apparent abnormalities function, developed lenticular opacities higher rate than controls. Our results suggest cataract phenotype represents multigenic disorder.