MDX TRANSGENIC MOUSE - RESTORATION OF RECOMBINANT DYSTROPHIN TO THE DYSTROPHIC MUSCLE

We report the restoration or the 430-kD dystrophin in mdx, the mouse m odel of Duchenne muscular dystrophy, by expression of a single-copy re combinant dystrophin transgene. Muscle-specific expression was achieve d using a creatine kinase promoter influenced by two enhancers. Immuno staining with anti-Xp21-coded dystrophin monoclonal antibodies showed that the recombinant dystrophin was localized to the muscle fiber memb rane. However, there was variability in the level of dystrophin expres sion in various animals with aging, between fast and slow muscles, and within different regions of the same muscle. Curiously, recombinant d ystrophin was relatively absent in the diaphragm muscle of these mdx t ransgenic animals. Our studies indicate that there is a direct correla tion between the level of muscle fibers expressing recombinant dystrop hin and the level of muscle fibers with peripheral nuclei, indicating an improvement in muscle pathology. These studies indicate that the re gional expression of recombinant dystrophin in dystrophic muscle leads to regional restoration of normal muscle morphology.