Role of FN14 in RNA Toxicity

描述(申请人提供)：强直性肌营养不良症(DM1)是成人和儿童最常见的肌营养不良症，是一种多系统、常染色体显性遗传疾病，由突变引起，导致产生对细胞有毒的突变RNA。目前还没有针对DM1的治疗方法。肌肉无力和消瘦是DM1的主要衰弱因素，但对DM1中的分子介质或肌肉病理知之甚少。我们已经建立了一个小鼠的RNA毒性模型，在这个模型中，我们已经证明了通过沉默有毒的RNA来逆转肌肉病理。我们已经使用这个模型来识别参与DM1中RNA毒性的新分子、机制和途径。这项特别的拨款是为了在我们的小鼠模型中使用遗传分析和治疗试验来解决我们已经确定的一种新分子的作用，以便评估其作为可行的治疗靶点的潜力。这一新发现为以下方面提供了新的机会：1)了解DM1的肌肉退化，也许还有心脏病理；2)开发治疗DM1肌肉营养不良的新疗法。

DESCRIPTION (provided by applicant): Myotonic dystrophy (DM1), the most common form of muscular dystrophy in adults and children, is a multi- systemic, autosomal dominant genetic disorder caused by a mutation that leads to the production of a mutant RNA that is toxic to cells. Currently there are no therapies for DM1. Muscle weakness and wasting are major debilitating factors in DM1 and yet very little is known about the molecular mediators or muscle pathology in DM1. We have developed a mouse model of RNA toxicity in which we have demonstrated reversal of muscle pathology by silencing the toxic RNA. We have used this model to identify new molecules, mechanisms and pathways involved in RNA toxicity in DM1. This particular grant is designed to use genetic analysis and therapeutic trials in our mouse model to address the role of one of the novel molecules that we have identified in order to assess its potential as a viable therapeutic target. This novel finding opens new opportunities for: 1) understanding muscle degeneration, and perhaps cardiac pathology in DM1 and 2) developing new therapies to treat muscular dystrophy in DM1.