Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype.
Proc Natl Acad Sci U S A
; 97(17): 9689-94, 2000 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-10931944
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Músculo Esquelético
/
Fibras Musculares Esqueléticas
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Distrofia Muscular de Duchenne
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Caveolinas
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article