MYOGENIC FACTORS: MUSCLE MATURATION AND REGENERATION

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DESCRIPTION (appended verbatim from investigator's abstract): Myf 5 and MyoD play critical roles in the specification and/or maintenance of muscle progenitor cells during development. While "knock out" mice provide a valuable tool for determining which functions of these factors are unique and the extent to which they might overlap, that Myf 5 null mice die at birth has limited the study of the maturation and regeneration of Myf 5 null muscles. By transplanting newborn Myf 5 null extensor digitorum longus (EDL) muscles into the bed of normal hosts (where these muscle regenerate and become innervated), we can compare these processes in Myf 5 and MyoD null mice. MyoD null muscles exhibits a regeneration deficit involving an inhibition of its satellite cells ability to undergo terminal differentiation; whereas, it is suggested that Myf 5 null myoblasts undergo precocious differentiation. Comparative studies of Myf 5 null, MyoD null and wild type muscle regeneration will be carried out with EM and morphometric analyses. The effect of the absence of Myf 5 on the number of satellite cell, satellite cell activation, proliferation and terminal differentiation will be assessed in regenerating muscle and in vitro. The effects of the absence of Myf 5 on muscle gene expression (e.g., genes encoding the MRFs, M cadhedrin, desmin, c met tyrosine kinase, etc.) in regenerating muscles and in cultures of myosatellite cells will be evaluated with competitive PCR and immunohistochemistry. Comparisons will be made with similar studies of normal and MyoD null regenerating muscle (Sabourin et al., 1999). The effect of the absence of Myf 5 on muscle phenotype will be evaluated with immunohistochemistry and gel electrophoresis. Muscle diseases are characterized by degeneration regeneration, with the regenerative effort being insufficient to keep pace with degeneration. These studies should provide clues to how it may be possible to increase muscle's regenerative response.