OVEREXPRESSION OF DYSTROPHIN IN TRANSGENIC MDX MICE ELIMINATES DYSTROPHIC SYMPTOMS WITHOUT TOXICITY

DUCHENNE and Becker muscular dystrophy (DMD and BMD) are X-linked rece ssive diseases caused by defective expression of dystrophin1,2. The md x mouse, an animal model for DMD, has a mutation that eliminates expre ssion of the 427K muscle and brain isoforms of dystrophin1,3,4. Althou gh these animals do not display overt muscle weakness or impaired move ment, the diaphragm muscle of the mdx mouse is severely affected and s hows progressive myofibre degeneration and fibrosis which closely rese mbles the human disease5,6. Here we explore the feasibility of gene th erapy for DMD by examining the potential of a full-length dystrophin t ransgene to correct dystrophic symptoms in mdx mice. We find that expr ession of dystrophin in muscles of transgenic mdx mice eliminates the morphological and immunohistological symptoms of muscular dystrophy. I n addition, overexpression of dystrophin prevents the development of t he abnormal mechanical properties associated with dystrophic muscle wi thout causing deleterious side effects. Our results provide functional evidence for the feasibility of gene therapy for DMD.