The overall goal of this project is to characterize the cellular expression of the human sarcomeric myosin heavy chain (MHC) gene family and begin to understand the relationship between diversity of cellular phenotype and MHC gene expression at the level of the individual myonucleus (myonucleus phenotype). The cellular MHC phenotype of normal differentiated, developing and diseased human muscle in vivo will be established by immunocytochemical detection of the MHC isoform protein; the myonuclear phenotype will in turn be determined in vitro the used of available cDNA probes for MHC isoform genes and the technique of in situ hybridization. Characterization of the myonuclear phenotype will test the hypothesis that myofibers are mosaic with respect to myonuclear MHC phenotype. Finally, the ontogeny of hypothesized myonuclear diversity will be studied further by exploiting the chick-quail chimera paradigm to create experimental mosaic myotubes in vitro. Such a model will permit more extensive study of myogenesis and gene regulation.
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