The role of dysferlin in skeletal muscle

缺乏蛋白质deferlin会导致肌肉营养不良，这是一种遗传性骨骼肌退行性疾病。有趣的是，由于缺铁蛋白缺乏引起的肌肉疾病直到成年早期才会发生。受影响的人在这个年龄段之前都非常活跃，体力正常，然后就会迅速发展为虚弱。许多患者在发病后几年内就失去了行走的能力。人们对deferlin在肌肉中的功能作用知之甚少，deferlin缺乏如何导致肌营养不良，或者为什么deferlin缺陷的肌肉在迅速出现症状之前功能正常。因此，这项研究的目的是描述异铁蛋白在正常和疾病骨骼肌中的作用。我们将在患者肌肉活检样本和培养中的患者肌肉细胞中检查铁缺乏的后果。我们将评估去铁蛋白在新的肌肉细胞融合和形成中的作用，研究去铁蛋白缺乏对肌膜修复的影响，并建立正常和突变的去铁蛋白是如何在肌肉细胞内产生、运输和降解的。这项研究将立即应用于诊断和咨询与卵泡发育障碍相关疾病的患者。此外，它还将提供关于疾病机制的有价值的信息，这对开发特定和成功的治疗方法至关重要。

Deficiency of the protein dysferlin causes muscular dystrophy, an inherited degenerative disorder of skeletal muscle. Interestingly, muscle disease due to deficiency of dysferlin does not occur until early adulthood. Affected individuals are very active with normal strength until this age and then there is rapid progression of weakness. Many patients lose the ability to walk within a few years of onset. Little is known about the functional role of dysferlin in muscle, how dysferlin deficiency results in muscular dystrophy, or why dysferlin-deficient muscle is functionally normal prior to the rapid onset of symptoms. Therefore, the goal of this study is to characterize the role of dysferlin in normal and diseased skeletal muscle. We will examine the consequence of dysferlin-deficiency in patient muscle biopsy samples and patient muscle cells in culture. We will assess the role of dysferlin in the fusion and formation of new muscle cells, examine the effect of dysferlin-deficiency on muscle membrane repair, and establish how normal and mutant dysferlin is made, trafficked and degraded within muscle cells. This research will have immediate applications to the diagnosis and counselling of patients with dysferlin-related disease. In addition it will provide valuable information concerning the mechanisms of disease, essential to the development of specific and successful therapies.