Role of FN14 in RNA Toxicity

描述（由申请人提供）：强直性肌营养不良（DM 1）是成人和儿童中最常见的肌营养不良形式，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DM 1的治疗方法。肌无力和消瘦是DM 1的主要衰弱因素，但对DM 1的分子介质或肌肉病理学知之甚少。我们已经开发了一种RNA毒性的小鼠模型，其中我们已经证明了通过沉默毒性RNA来逆转肌肉病理。我们已经使用这个模型来识别DM 1中涉及RNA毒性的新分子、机制和途径。这项特殊的资助旨在使用我们的小鼠模型中的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，以评估其作为可行治疗靶点的潜力。这一新的发现为以下方面提供了新的机会：1）了解DM 1中的肌肉变性，以及可能的心脏病理学; 2）开发治疗DM 1中肌营养不良症的新疗法。

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.