Abstract
It recently was reported that Duchenne muscular dystrophy (DMD) patients and mdx mice have elevated levels of caveolin-3 expression in their skeletal muscle. However, it remains unknown whether increased caveolin-3 levels in DMD patients contribute to the pathogenesis of DMD. Here, using a genetic approach, we test this hypothesis directly by overexpressing wild-type caveolin-3 as a transgene in mice. Analysis of skeletal muscle tissue from caveolin-3- overexpressing transgenic mice reveals: (i) a dramatic increase in the number of sarcolemmal muscle cell caveolae; (ii) a preponderance of hypertrophic, necrotic, and immature/regenerating skeletal muscle fibers with characteristic central nuclei; and (iii) down-regulation of dystrophin and beta-dystroglycan protein expression. In addition, these mice show elevated serum creatine kinase levels, consistent with the myo-necrosis observed morphologically. The Duchenne-like phenotype of caveolin-3 transgenic mice will provide an important mouse model for understanding the pathogenesis of DMD in humans.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Caveolin 3
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Caveolins*
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Cell Nucleus / pathology
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Creatine Kinase / blood
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Cytoskeletal Proteins / metabolism
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Disease Models, Animal
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Down-Regulation
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Dystroglycans
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Dystrophin / metabolism
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Female
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Hindlimb / physiopathology
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Immunohistochemistry
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Male
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Membrane Glycoproteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Membrane Proteins / ultrastructure
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Mice
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Mice, Inbred mdx
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Mice, Transgenic
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Microscopy, Electron
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Muscle Fibers, Skeletal / metabolism*
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Muscle Fibers, Skeletal / pathology
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Muscle Fibers, Skeletal / physiology
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Muscle, Skeletal / metabolism*
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiopathology
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Muscular Dystrophy, Duchenne / genetics
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Muscular Dystrophy, Duchenne / metabolism
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Muscular Dystrophy, Duchenne / pathology
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Muscular Dystrophy, Duchenne / physiopathology*
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Necrosis
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Phenotype
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Rotation
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Sarcolemma / pathology
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Transgenes / genetics
Substances
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Cav3 protein, mouse
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Caveolin 3
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Caveolins
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Cytoskeletal Proteins
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Dystrophin
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Membrane Glycoproteins
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Membrane Proteins
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Dystroglycans
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Creatine Kinase