Muscular Dystrophy Cooperative Research Center

罗切斯特大学MDCRC的主要优势是拥有一大批积极性高、特征鲜明的强直性肌营养不良（DM 1和DM 2）和面肩肱型肌营养不良（FSHD）患者，他们渴望支持基础研究并参与临床研究，以及一群在这些疾病方面具有长期专业知识的热情研究人员。这些资产使我们使“显性遗传性肌营养不良症：病理生理学和治疗”成为我们3个月的主要焦点。 科学项目和2个科学核心。我们的主要重点是DM 1和FSHD。项目1探索“RNA毒性和肌盲蛋白在DM病理生理学中的作用”。使用肌盲敲除小鼠和骨骼肌氯离子通道选择性剪接的研究，项目1检查了强直性肌营养不良症的毒性RNA模型。它测试了DM 1和DM 2中异常扩增的mRNA等位基因隔离某些dsRNA结合因子（肌盲蛋白）并导致肌强直和肌病的假设。项目2研究了DM 1的潜在新治疗方法，并希望证明SomatoKine（与重组IGF结合蛋白-3复合的胰岛素样生长因子-1 [IGF 1]）是安全的， 耐受性良好，有望成为一种治疗方法该项目测试了IGF 1激活不足导致DM 1萎缩的假设，并且维持高水平的IGF 1将纠正这种缺陷。项目3致力于增加我们对FSHD的分子和细胞病理生理学的了解。它使用肌肉活检标本的微阵列分析来检验两个假设：在FSHD中：a）D4 Z4异染色质重复序列的缺失不会改变相邻的4 q35基因;和，B）平滑肌基因的异常过表达是病理生理学的重要贡献者。一个科学核心是一个成像中心。它提供了专门的肌肉组织化学和免疫学技术，荧光原位杂交， 共聚焦显微镜和电子显微镜。项目1和项目3广泛使用该核心。另一个科学核心是一个资源库，用于研究肌肉营养不良。该核心主张：a）DM 1和FSHD的成肌细胞系; B）转基因模型细胞系; c）质粒; d）抗体; e）尸检组织DM 1;和f）DM 1和FSHD患者的基因表达数据。项目1、2和3与存储库核心交互，此核心将与其他MDCRC交互。

A major strength of the University of Rochester MDCRC is having a large group of highly motivated, well-characterized patients with myotonic dystrophy (DM1 & DM2) and facioscapulohumeral muscular dystrophy (FSHD), eager to support basic research and participate in clinical studies, and a group of enthusiastic investigators with a longstanding expertise in these diseases. These assets have led us to make "The Dominantly Inherited Muscular Dystrophies: Pathophysiology and Treatment" the major focus of our 3 scientific projects and 2 scientific cores. Our primary emphases are on DM1 and FSHD. Project 1 explores the "Role of RNA Toxicity and Muscleblind Proteins in the Pathophysiology of DM". Using muscleblind knockout mice and studies of alternative splicing of the skeletal muscle chloride channel Project 1 examines a toxic RNA model for the myotonic dystrophies. It tests the hypothesis that the abnormally expanded mRNA alleles in DM1 & DM2 sequester certain dsRNA-binding factors, the muscleblind proteins, and that this leads to myotonia and myopathy. Project 2 investigates a potential new treatment in DM1 and hopes to prove that SomatoKine (insulin-like growth factor-1 [IGF1] complexed with recombinant IGF binding protein-3) is safe, well-tolerated, and promising as a therapy. This project tests the hypothesis that deficient activation by IGF1 contributes to the atrophy in DM1, and that maintaining high blood levels of IGF1 will correct this deficiency. Project 3 strives to increase our knowledge of the molecular and cellular pathophysiology of FSHD. It uses microarray analysis of muscle biopsy specimens to test two hypotheses: in FSHD: a) deletion of D4Z4 heterochromatic repeats does not alter adjacent 4q35 genes; and, b) aberrant overexpression of smooth muscle genes is an important contributor to the pathophysiology. One Scientific Core is an Imaging Center. It provides specialized muscle histochemical and immunological techniques, fluorescent in situ hybridization, confocal microscopy, and electron microscopy. Projects 1 & 3 make extensive use of this Core. The other Scientific Core is a Repository of resources for research on Muscular Dystrophy. This Core maintains: a) myoblast cell lines for DM1 and FSHD; b) transgenic model cell lines; c) plasmids; d) antibodies; e) autopsy tissue DM1; and f) gene expression data on DM1 & FSHD patients. Projects 1, 2, & 3 interact with the Repository Core and this Core will interact with the other MDCRCs.