Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype

It recently was reported that Duchenne muscular dystrophy (DMD) patients an d mdx mice have elevated levels of caveolin-3 expression in their skeletal muscle. However, it remains unknown whether increased caveolin-3 levels in DMD patients contribute to the pathogenesis of DMD. Here, using a genetic a pproach, we test this hypothesis directly by overexpressing wild-type caveo lin-3 as a transgene in mice, Analysis of skeletal muscle tissue from caveo lin-3- overexpressing transgenic mice reveals: (i) a dramatic increase in t he number of sarcolemmal muscle cell caveolae; (ii) a preponderance of hype rtrophic, necrotic, and immature/regenerating skeletal muscle fibers with c haracteristic central nuclei; and (iii) down-regulation of dystrophin and b eta-dystroglycan protein expression. In addition, these mice show elevated serum creatine kinase revels, consistent with the myo-necrosis observed mor phologically. The Duchenne-like phenotype of caveolin-3 transgenic mice wil l provide an important mouse model for understanding the pathogenesis of DM D in humans.