Caveolin-3 Null Mice Show a Loss of Caveolae, Changes in the Microdomain Distribution of the Dystrophin-Glycoprotein Complex, and T-tubule Abnormalities

Ferruccio Galbiati, Jeffrey A. Engelman, Daniela Volonte, Xiao Lan Zhang, Carlo Minetti, Maomi Li, Harry Hou, Burkhard Kneitz, Winfried Edelmann, Michael P. Lisanti

Research output: Contribution to journalArticle

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Abstract

Caveolin-3, a muscle-specific caveolin-related protein, is the principal structural protein of caveolae membrane domains in striated muscle cells. Recently, we identified a novel autosomal dominant form of limb-girdle muscular dystrophy (LGMD-1C) in humans that is due to mutations within the coding sequence of the human caveolin-3 gene (3p25). These LGMD-1C mutations lead to an ∼95% reduction in caveolin-3 protein expression, i.e. a caveolin-3 deficiency. Here, we created a caveolin-3 null (CAV3 -/-) mouse model, using standard homologous recombination techniques, to mimic a caveolin-3 deficiency. We show that these mice lack caveolin-3 protein expression and sarcolemmal caveolae membranes. In addition, analysis of skeletal muscle tissue from these caveolin-3 null mice reveals: (i) mild myopathic changes; (ii) an exclusion of the dystrophin-glycoprotein complex from lipid raft domains; and (iii) abnormalities in the organization of the T-tubule system, with dilated and longitudinally oriented T-tubules. These results have clear mechanistic implications for understanding the pathogenesis of LGMD-1C at a molecular level.

Original languageEnglish (US)
Pages (from-to)21425-21433
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
StatePublished - Jun 15 2001

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Caveolin 3
Caveolae
Dystrophin
Glycoproteins
Muscle
Caveolins
Proteins
Membranes
Limb-Girdle Muscular Dystrophies
Mutation
Striated Muscle
Homologous Recombination
Muscle Cells
Genes
Cells
Membrane Proteins
Skeletal Muscle
Tissue
Lipids

ASJC Scopus subject areas

  • Biochemistry

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Caveolin-3 Null Mice Show a Loss of Caveolae, Changes in the Microdomain Distribution of the Dystrophin-Glycoprotein Complex, and T-tubule Abnormalities. / Galbiati, Ferruccio; Engelman, Jeffrey A.; Volonte, Daniela; Zhang, Xiao Lan; Minetti, Carlo; Li, Maomi; Hou, Harry; Kneitz, Burkhard; Edelmann, Winfried; Lisanti, Michael P.

In: Journal of Biological Chemistry, Vol. 276, No. 24, 15.06.2001, p. 21425-21433.

Research output: Contribution to journalArticle

Galbiati, Ferruccio ; Engelman, Jeffrey A. ; Volonte, Daniela ; Zhang, Xiao Lan ; Minetti, Carlo ; Li, Maomi ; Hou, Harry ; Kneitz, Burkhard ; Edelmann, Winfried ; Lisanti, Michael P. / Caveolin-3 Null Mice Show a Loss of Caveolae, Changes in the Microdomain Distribution of the Dystrophin-Glycoprotein Complex, and T-tubule Abnormalities. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 24. pp. 21425-21433.
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