Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype

Ferruccio Galbiati, Daniela Volonté, Jeffrey B. Chu, Maomi Li, Samson W. Fine, Maofu Fu, Jorge Bermudez, Marina Pedemonte, Karen M. Weidenheim, Richard G. Pestell, Carlo Minetti, Michael P. Lisanti

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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 β-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.

Original languageEnglish (US)
Pages (from-to)9689-9694
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number17
StatePublished - Aug 15 2000

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Caveolin 3
Skeletal Muscle Fibers
Duchenne Muscular Dystrophy
Phenotype
Transgenic Mice
Skeletal Muscle
Dystroglycans
Inbred mdx Mouse
Caveolae
Dystrophin
Creatine Kinase
Transgenes
Muscle Cells
Type 2C Limb-girdle muscular dystrophy
Necrosis
Down-Regulation
Muscles
Serum

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype. / Galbiati, Ferruccio; Volonté, Daniela; Chu, Jeffrey B.; Li, Maomi; Fine, Samson W.; Fu, Maofu; Bermudez, Jorge; Pedemonte, Marina; Weidenheim, Karen M.; Pestell, Richard G.; Minetti, Carlo; Lisanti, Michael P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 17, 15.08.2000, p. 9689-9694.

Research output: Contribution to journalArticle

Galbiati, F, Volonté, D, Chu, JB, Li, M, Fine, SW, Fu, M, Bermudez, J, Pedemonte, M, Weidenheim, KM, Pestell, RG, Minetti, C & Lisanti, MP 2000, 'Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 17, pp. 9689-9694.
Galbiati, Ferruccio ; Volonté, Daniela ; Chu, Jeffrey B. ; Li, Maomi ; Fine, Samson W. ; Fu, Maofu ; Bermudez, Jorge ; Pedemonte, Marina ; Weidenheim, Karen M. ; Pestell, Richard G. ; Minetti, Carlo ; Lisanti, Michael P. / Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 17. pp. 9689-9694.
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