Dystrophic Cardiomyopathies in mdx

描述（由申请人提供）：心肌病在杜氏肌营养不良症（DMD）患者中非常常见，90%的患者发生。DMD是由于缺乏肌营养不良蛋白（一种主要在横纹肌中发现的大蛋白质）所致。DMD对骨骼肌的影响已经有了很好的记录，但对心肌的影响在很大程度上尚未探索。mdx小鼠是DMD的模型，仅显示轻度病理，尽管在老年小鼠中隔膜受到严重影响。最近的证据表明，mdx小鼠的心脏特别容易随着工作量的增加而受损。本研究通过测试以下假设的具体目标来考察这一现象： 1)对心脏施加压力将导致mdx心脏的心肌病，而野生型小鼠则不受影响。将通过侵入性和非侵入性技术监测心脏功能的这种下降。 2)mdx小鼠的营养不良性心肌病可以在基因操作后通过在心肌细胞中表达功能性肌营养不良蛋白的转基因或腺病毒载体来预防或逆转。

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.