Abstract
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.
Overview summary
The restoration of recombinant dystrophin to the dystrophic muscle of the mdx mouse was achieved through transgenic techniques. By immunostaining, regional expression of the 430-kD recombinant dystrophin was observed in muscle fibers membrane of the mdx transgenic mouse. The expression of recombinant dystrophin can lead to restoration of a normal muscle morphology based on dystrophin-positive fibers, peripheral nuclei, and the lack of interstitial defects, normally observed in mdx mouse muscle.
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