Dystrophic Cardiomyopathies in mdx

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DESCRIPTION (provided by applicant): Cardiomyopathies are very common in patients with Duchenne's Muscular Dystrophy (DMD), occurring in 90% patients. DMD results from the absence of dystrophin, a large protein found primarily in striated muscle. The effects of DMD on skeletal muscle have been well documented, but the effects on cardiac muscle are largely unexplored. The mdx mouse is a model of DMD, displaying only mild pathology, although the diaphragm is severely affected in older mice. Recent evidence suggests that the heart of the mdx mouse is particularly susceptible to damage with an increase in workload. This study examines this phenomenon through the specific aims testing the following hypotheses: 1) Stressing the heart will result in a cardiomyopathy in the mdx heart, while wild type mice remain unaffected. This decline in cardiac function will be monitored by both invasive and non-invasive techniques. 2) The dystrophic cardiomyopathy of the mdx mouse can be prevented or reversed following genetic manipulations, by either transgenic or by adenoviral vectors, that express functional dystrophin in cardiomyocytes.