Muscular Dystrophy Cooperative Research Center

罗切斯特大学MDCRC的一个主要优势是拥有一大批积极进取、特征良好的强直性肌营养不良(DM1和DM2)和面肩肩周肌营养不良(FSHD)患者，他们渴望支持基础研究和参与临床研究，以及一批在这些疾病方面拥有长期专业知识的热情研究人员。这些资产使我们将“显性遗传性肌营养不良症：病理生理学和治疗”作为我们3个项目的主要重点 科学项目和2个科学核心。我们的主要重点是DM1和FSHD。项目1探讨了“RNA毒性和盲蝇蛋白在糖尿病的病理生理学中的作用”。利用肌肉失明基因敲除小鼠和骨骼肌氯离子通道选择性剪接的研究，项目1检验了强直性肌营养不良症的有毒RNA模型。它测试了一种假设，即DM1和DM2中异常扩大的mRNA等位基因隔离了某些dsRNA结合因子和肌肉盲蛋白，从而导致肌强直和肌病。项目2研究了一种潜在的治疗DM1的新方法，并希望证明SomatoKine(胰岛素样生长因子-1[IGF1]与重组IGF结合蛋白-3复合)是安全的， 耐受性良好，作为一种治疗方法前景看好。该项目测试了IGF1激活缺陷导致DM1萎缩的假设，以及维持血液中IGF1的高水平将纠正这一缺陷。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)D4Z4异色重复序列的缺失不会改变相邻的4q35基因；以及b)平滑肌基因的异常过表达是导致FSHD病理生理的重要因素。One Science Core是一个成像中心。它提供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3广泛使用了这一核心。另一个科学核心是肌营养不良症研究的资源库。该中心维护：a)DM1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DM1；以及f)DM1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，该核心将与其他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.