Muscular dysgenesis: a model system for studying skeletal muscle development

Muscular dysgenesis, caused by an autosomal recessive lethal mutation ( mdg ) in mice, is characterized by an absence of contraction of skeletal muscle. A historical review of the investigation of this disorder is presented. The early studies of the morphological and physiological aspects of the disorder in vivo and in vitro presented evidence for dysfunction in the skeletal muscle excitation‐contraction (E‐C) system, and thus suggested that skeletal muscle was the primary target of dysfunction in dysgenesis. Subsequent evidence, including the phenomenon of rescue (restoration of contraction) of dysgenic muscle in culture by spinal cord cells, argued for involvement of the nervous system in the disorder. Experiments demonstrating that dysgenic muscle lacks the slow calcium current associated with E‐C coupling, and the protein (the dihydropyridine receptor) also associated with such coupling, led to the discovery of the probable site of the mutation: the gene for the α 1 subunit of the dihydropyridine receptor. The neuronal involvement hypothesis was further countered by several lines of evidence, including the phenomenon of fusion of nonmyogenic normal cells with dysgenic myotubes in cocultures of normal cells and dysgenic muscle. The use of the mutant as a model for studying the development of normal skeletal muscle is discussed and future avenues of research are explored.— P owell , J. A. Muscular dysgenesis: a model system for studying skeletal muscle development. FASEB J. 4: 2798‐2808; 1990.