Mdx transgenic mouse: restoration of recombinant dystrophin to the dystrophic muscle.

We report the restoration of the 430-kD dystrophin in mdx, the mouse model of Duchenne muscular dystrophy, by expression of a single-copy recombinant dystrophin transgene. Muscle-specific expression was achieved using a creatine kinase promoter influenced by two enhancers. Immunostaining with anti-Xp21-coded dystrophin monoclonal antibodies showed that the recombinant dystrophin was localized to the muscle fiber membrane. However, there was variability in the level of dystrophin expression in various animals with aging, between fast and slow muscles, and within different regions of the same muscle. Curiously, recombinant dystrophin was relatively absent in the diaphragm muscle of these mdx transgenic animals. Our studies indicate that there is a direct correlation between the level of muscle fibers expressing recombinant dystrophin and the level of muscle fibers with peripheral nuclei, indicating an improvement in muscle pathology. These studies indicate that the regional expression of recombinant dystrophin in dystrophic muscle leads to regional restoration of normal muscle morphology.