EXPRESSION OF FULL-LENGTH AND TRUNCATED DYSTROPHIN MINI-GENES IN TRANSGENIC MDX MICE

Duchenne and Becker muscular dystrophy are caused by defects in the dy strophin gene, and are candidates for treatment by gene therapy, We ha ve shown previously that overexpression of a full-length dystrophin cD NA prevents the development of dystrophic symptoms in mdx mice, We sho w here that this functional correction can be achieved by expressing t he full-length muscle isoform at a lower level than is present in cont rol animals, Gene therapy for DMD may necessitate the use of truncated dystrophin mini-genes to accommodate the limited cloning capacity of current-generation viral delivery vectors, We have constructed both mu rine and human mini-genes deleted for exons 17-48, and have demonstrat ed that expression of either mini-gene can almost completely prevent t he development of dystrophic symptoms in transgenic mdx mice, These re sults suggest that viral-mediated expression of moderate levels of a t runcated dystrophin could be an effective treatment for DMD.