Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation

Here, we examine the role of "non-muscle" caveolins (Cav-1 and Cav-2) in skeletal muscle biology. Our results indicate that skeletal muscle fibers from male Cav-1(-/-) and Cav-2(-/-) mice show striking abnormalities, such as tubular aggregates, mitochondrial proliferation/aggregation, and...

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Published in:The American journal of pathology Vol. 170; no. 1; p. 316
Main Authors: Schubert, William, Sotgia, Federica, Cohen, Alex W, Capozza, Franco, Bonuccelli, Gloria, Bruno, Claudio, Minetti, Carlo, Bonilla, Eduardo, Dimauro, Salvatore, Lisanti, Michael P
Format: Journal Article
Language:English
Published: United States 01.01.2007
Subjects:
Animals
Cadherins - biosynthesis
Caveolin 1 - deficiency
Caveolin 1 - genetics
Caveolin 2 - deficiency
Caveolin 2 - genetics
Disease Models, Animal
Electron Transport Complex IV - analysis
Genetic Predisposition to Disease
Male
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Mitochondria, Muscle - metabolism
Mitochondria, Muscle - ultrastructure
Muscle Fibers, Skeletal - metabolism
Muscle Fibers, Skeletal - ultrastructure
Muscle, Skeletal - abnormalities
Muscle, Skeletal - metabolism
Muscle, Skeletal - ultrastructure
Muscular Diseases - genetics
Muscular Diseases - metabolism
Muscular Diseases - pathology
Myoblasts - metabolism
Myoblasts - pathology
ISSN:0002-9440
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Summary:Here, we examine the role of "non-muscle" caveolins (Cav-1 and Cav-2) in skeletal muscle biology. Our results indicate that skeletal muscle fibers from male Cav-1(-/-) and Cav-2(-/-) mice show striking abnormalities, such as tubular aggregates, mitochondrial proliferation/aggregation, and increased numbers of M-cadherin-positive satellite cells. Notably, these skeletal muscle defects were more pronounced with increasing age. Because Cav-2-deficient mice displayed normal expression levels of Cav-1, whereas Cav-1-null mice exhibited an almost complete deficiency in Cav-2, these skeletal muscle abnormalities seem to be due to loss of Cav-2. Thus, Cav-2(-/-) mice represent a novel animal model-and the first genetically well-defined mouse model-that can be used to study the pathogenesis of tubular aggregate formation, which remains a poorly understood age-related skeletal muscle abnormality. Finally, because Cav-1 and Cav-2 were not expressed within mature skeletal myofibers, our results indicate that development of these abnormalities probably originates in stem/precursor cells, such as satellite cells or myoblasts. Consistent with this hypothesis, skeletal muscle isolated from male Cav-3(-/-) mice did not show any of these abnormalities. As such, this is the first study linking stem cells with the genesis of these intriguing muscle defects.
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ISSN:0002-9440
DOI:10.2353/ajpath.2007.060687