MUSCLE SATELLITE CELL: REACTION TO DISEASE AND TRAUMA

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It is proposed to study, in depth, genetically determined myopathies, with particular emphasis on the following objectives; 1. Elucidation of the mechanism(s) responsible for determining whether genetically dystrophic (dy) murine muscle expresses or fails to express the dystrophic phenotype. 2. Determination of whether the inhibition of the degeneration- regeneration cycle which occurs when dystrophic (dy) muscle is transiently denervated is unique to this dystrophic mutant or whether a similar modification will occur in other diverse genetically determined myopathies (e.g., the mdx mouse and the dystrophic hamster). 3. Determination of the effect of inhibition of the degeneration- regeneration cycle of dystrophic (dy) myofibers on the development of proliferative senescence of myosatellite cells of these muscles. Determination whether the proliferative senescence of dy myosatellite cells in vitro is a result of the exhaustion of the mitotic capability of these cells during the early stage of the disease process or whether there is a primary defect in the myosatellite cells of dy muscles. 4. Evaluation of the extent of regeneration which occurs in the mdx mutant mouse. Evaluation of the mitotic capability of the myosatellite cells of the mdx muscle using clonal analysis.