INCREASED A7/B1 INTEGRIN SIGNALING SECONDARY TO DAPC DISSOCIATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 COBRE项目2研究了肌营养不良蛋白和整合素复合物的通讯调节肢带肌营养不良2F的δ-肌聚糖敲除小鼠模型中的扩张型心肌病的假设。我们的小鼠群体自成立以来发展迅速，8-20-08，建立了两个三角洲来自伊丽莎白·麦克纳利，医学博士，博士;芝加哥大学。我们于2008年11月20日从Dean Burkin，Ph.D（内华达州转基因机构）建立了3对α 7整联蛋白敲除小鼠的育种对。我们在09年3月13日开始了两次<$7 KO（B）X <$SG KO（@）交叉。这些杂交是成功的，两对都产生了活的幼崽。这些幼仔将于2009年4月26日和2009年4月28日断奶，并成熟以评估扩张型心肌病。我们预测，这种新的交叉的特点将产生独特的信息，将指导发展的治疗方法，以扩张型心肌病患者的肌营养不良症。 我们开发了一个程序来检查这些肌肉萎缩症小鼠模型的骨骼肌发育。这补充了我们对扩张型心肌病的研究，因为我们将研究骨骼肌分化的药理学方法。具体来说，我们将研究的假设，即蛋白激酶，GSK-3的失活，逆转的负调控的转录因子是由GSK-3介导的。这一假设是NIH挑战基金的重点，题为“GSK-3失活和肌肉营养不良症中的骨骼肌再生”，该基金是针对广泛的挑战领域再生医学而提交的。

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 delta-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 deltasarcoglycan 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.