Functional characteristics of dystrophic skeletal muscle: insights from animal models.
Muscular dystrophies are a clinically and genetically heterogeneous group of disorders that show myofiber degeneration and regeneration. Identification of animal models of muscular dystrophy has been instrumental in research on the pathogenesis, pathophysiology, and treatment of these disorders. We review our understanding of the functional status of dystrophic skeletal muscle from selected animal models with a focus on 1) the mdx mouse model of Duchenne muscular dystrophy, 2) the Bio 14.6 delta-sarcoglycan-deficient hamster model of limb-girdle muscular dystrophy, and 3) transgenic null mutant murine lines of sarcoglycan (alpha, beta, delta, and gamma) deficiencies. Although biochemical data from these models suggest that the dystrophin-sarcoglycan-dystroglycan-laminin network is critical for structural integrity of the myofiber plasma membrane, emerging studies of muscle physiology suggest a more complex picture, with specific functional deficits varying considerably from muscle to muscle and model to model. It is likely that changes in muscle structure and function, downstream of the specific, primary biochemical deficiency, may alter muscle contractile properties.
Watchko
Jon F
JF
Department of Pediatrics, Magee-Women's Research Institute, Duchenne Muscular Dystrophy Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. jwatchko@mail.magee.edu
O'Day
Terrence L
TL
Hoffman
Eric P
EP
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology*