INCREASED A7/B1 INTEGRIN SIGNALING SECONDARY TO DAPC DISSOCIATION

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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.