Molecular analysis of the function of a muscle-specific caveolar protein

肌肉萎缩症是人类最常见和最衰弱的遗传性疾病之一。肌肉萎缩症患者的肌肉极易受到损伤，导致肌肉萎缩。为了了解肌肉萎缩症并设计治疗方法，研究人员必须详细了解肌肉细胞表面膜的工作原理。小窝是覆盖整个肌纤维表面的小凹坑。肌小窝的主要蛋白质是小窝蛋白-3，这种蛋白质的突变会导致某些形式的肌肉萎缩。本提案旨在使用多种策略来检查该蛋白质的功能。小鼠体内的小窝蛋白-3基因会被破坏，从而产生缺乏这种蛋白质的小鼠。研究人员将对这些小鼠的肌肉进行检查，以观察缺乏这种蛋白质对肌肉功能的影响，以及这种肌肉是否与肌肉萎缩症患者的肌肉相似。这些小鼠的肌肉将被用于设计疾病的治疗方法。此外，我们将寻找与caveolin-3一起工作的蛋白质，以了解蛋白质如何在健康和患病肌肉中起作用。

Muscular dystrophy is one of the most common and most debilitating inherited diseases in humans. Muscle from patients with muscular dystrophy is highly susceptible to damage leading to muscle wasting. In order to understand muscular dystrophy and to design therapeutic treatments, it is essential that researchers gain a detailed understanding of the workings of the muscle cell surface membrane. Caveolae are small pits which cover the entire surface of the muscle fibre. The major protein of muscle caveolae is caveolin-3, and mutations in this protein cause some forms of muscular dystrophy. This proposal aims to examine the function of this protein using a number of strategies. The caveolin-3 gene will be disrupted in mice to produce mice which lack this protein. The muscle from these mice will then be examined to see what effect the lack of this protein has on muscle function and whether this muscle is similar to that in patients with muscular dystrophy. The muscle from these mice will then be used to design treatments for the disease. In addition, we will search for proteins which work together with caveolin-3 in order to understand how the protein works in healthy and diseased muscle.