INCREASED A7/B1 INTEGRIN SIGNALING SECONDARY TO DAPC DISSOCIATION

DAPC 解离后 A7/B1 整合素信号传导增强

• 批准号: 7959742
• 负责人: STEPHEN C ARMSTRONG
• 金额: $ 21.83万
• 依托单位: SANFORD RESEARCH/USD
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959742
• 关键词: Area; Breeding; Cardiovascular system; Centers of Research Excellence; Chicago; Communication; Complement; Complex; Computer Retrieval of Information on Scientific Projects Database; Dilated Cardiomyopathy; Dissociation; Doctor of Medicine; Doctor of Philosophy; Dystrophin; Funding; Glycogen Synthase Kinase 3; Grant; Institution; Integrins; Knock-out; Knockout Mice; Life; Limb-Girdle Muscular Dystrophies; Mediating; Mus; Muscle Development; Muscular Dystrophies; Nevada; Patients; Protein Kinase; Regenerative Medicine; Regulation; Research; Research Personnel; Resources; Sarcoglycans; Secondary to; Signal Transduction; Skeletal Muscle; Source; Transgenic Organisms; United States National Institutes of Health; Universities; Weaning; human ITGA7 protein; mouse model; muscle regeneration; muscular dystrophy mouse model; novel; programs; pup; response; skeletal muscle differentiation; therapeutic development; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. COBRE Project 2 examines the hypothesis that communication of the dystrophin and integrin complexes regulates dilated cardiomyopathy in a ¿-sarcoglycan knock out mouse model of Limb Girdle Muscular Dystrophy 2F. Our mouse colony has developed rapidly since it inception, 8-20-08, with the establishment of two ¿sarcoglycan knock out breeding pairs from Elizabeth McNally, M.D., Ph.D; University of Chicago. We established three breeding pairs of alpha 7 integrin knock-out mice from Dean Burkin, Ph.D (Nevada Transgenic Facility) on 11-20-08. We initiated two ¿7 KO (B) X ¿SG KO (@) crosses on 3-13-09. These crosses were successful with both pairings producing live pups. These pups will be weaned on 4-26-09 and 4-28-09 and matured for assessment of dilated cardiomyopathy. We predict that the characterization of this novel cross will yield unique information that will guide the development of therapeutic approaches to dilated cardiomyopathy in patients with muscular dystrophy. We developed a program that examines skeletal muscle development in these mouse models of muscular dystrophy. This complements our studies on dilated cardiomyopathy in that we will examine pharmacologic approaches to the differentiation of skeletal muscle. Specifically, we will examine the hypothesis that inactivation of the protein kinase, GSK-3, reverses the negative regulation of transcription factors that is mediated by GSK-3. This hypothesis is the focus of an NIH Challenge Grant, entitled "GSK-3 Inactivation and Skeletal Muscle Regeneration in Muscular Dystrophy", that was submitted in response to the broad challenge area, Regenerative Medicine.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 Cobre Project 2研究了以下假设：肌营养不良蛋白和整联蛋白复合物的通信调节sarcoglycun中的扩张性心肌病的扩张，将肢体腰带肌营养不良2F的小鼠模型敲除了小鼠模型。自成立以来，我们的小鼠菌落已经迅速发展，即8-20-08，建立了两个sarcoglycan敲除伊丽莎白·麦克纳利（Elizabeth McNally），医学博士，博士学位的繁殖对；芝加哥大学。我们于11-20-08建立了来自Dean Burkin博士（内华达州转基因设施）的三对alpha 7整合素敲除小鼠。我们在3-13-09启动了两个7 ko（b）x€sg ko（@）。这些十字架成功，两对生产活幼崽。这些幼崽将在4-26-09和4-28-09断奶，并成熟以评估扩张的心肌病。我们预测，这种新颖的十字架的表征将产生独特的信息，这将指导肌肉营养不良患者的心肌病的治疗方法的发展。 我们开发了一个程序，该程序在这些肌肉营养不良的小鼠模型中检查了骨骼肌的发育。这符合我们对扩张心肌病的研究，因为我们将研究骨骼肌分化的药物方法。具体而言，我们将研究以下假设：GSK-3蛋白激酶的失活反转了由GSK-3介导的转录因子的负调控。该假设是NIH挑战补助金的重点，标题为“ GSK-3失活和骨骼肌再生肌肉营养不良”，这是响应广泛的挑战领域，再生医学的响应。