MICE LACKING THE MYOTONIC-DYSTROPHY PROTEIN-KINASE DEVELOP A LATE-ONSET PROGRESSIVE MYOPATHY

Myotonic dystrophy (DM) is an autosomal dominant disorder resulting fr om the expansion of a CTG repeat in the 3' untranslated region of a pu tative protein kinase (DMPK). To elucidate the role of DMPK in DM path ogenesis we have developed Dmpk deficient (Dmpk-/-) mice. Dmpk-/- mice develop a late-onset, progressive skeletal myopathy that shares some pathological features with DM. Muscles from mature mice show variation in fibre size, increased fibre degeneration and fibrosis. Adult Dmpk- /- mice show ultrastructural changes in muscle and a 50% decrease in f orce generation compared to young mice. Our results indicate that DMPK may be necessary for the maintenance of skeletal muscle structure and function and suggest that a decrease in DMPK levels may contribute to DM pathology.