Dystrophic Cardiomyopathies in mdx

描述(申请人提供)：心肌病在Duchenne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造成的，肌营养不良蛋白是一种主要在横纹肌中发现的大型蛋白质。DMD对骨骼肌的影响已经有了很好的文献记载，但对心肌的影响在很大程度上还没有被探索。MDX小鼠是DMD的一个模型，只表现出轻微的病理，尽管年长的小鼠的横隔膜受到严重影响。最近的证据表明，随着工作负荷的增加，MDX小鼠的心脏特别容易受到损害。本研究通过检验以下假设的具体目的来检验这一现象： 1)对心脏施加压力会导致MDX心脏的心肌病，而野生型小鼠则不受影响。这种心功能的下降将通过有创和非侵入性技术进行监测。 2)mdx鼠的营养不良心肌病可以通过转基因或通过在心肌细胞中表达功能性dystrophin的腺病毒载体的基因操作来预防或逆转。

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.