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Methods to Assess Subcellular Compartments of Muscle in C. elegans
Published on: November 13, 2014
Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous skeletal muscle abnormalities, with tubular
William Schubert1, Federica Sotgia, Alex W Cohen
1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
Abstract:
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.
Insights
Loss of caveolin-2 (Cav-2) in mice causes age-related skeletal muscle defects, including tubular aggregates and mitochondrial issues. These abnormalities likely originate in stem cells, offering a new model for studying muscle aging.
Area of Science:
- Cell Biology
- Muscle Biology
- Aging Research
Background:
- Caveolins (Cav-1, Cav-2) are proteins typically found in non-muscle tissues.
- Their specific roles in skeletal muscle biology, particularly in aging and disease, are not well understood.
- Age-related skeletal muscle abnormalities like tubular aggregates are poorly understood.
Purpose of the Study:
- To investigate the function of non-muscle caveolins (Cav-1 and Cav-2) in skeletal muscle.
- To determine the cause of age-related skeletal muscle defects.
- To establish a new animal model for studying tubular aggregate formation.
Main Methods:
- Analysis of skeletal muscle from male Cav-1 knockout (Cav-1(-/-)) and Cav-2 knockout (Cav-2(-/-)) mice.
- Comparison of muscle phenotypes between knockout and wild-type mice, including assessment of age-related changes.
- Examination of satellite cell populations and mitochondrial morphology.
- Investigation of Cav-1 and Cav-2 expression in mature myofibers versus stem/precursor cells.
Main Results:
- Skeletal muscle fibers from Cav-1(-/-) and Cav-2(-/-) mice exhibited abnormalities: tubular aggregates, mitochondrial proliferation/aggregation, and increased M-cadherin-positive satellite cells.
- These defects were more pronounced with increasing age.
- Skeletal muscle abnormalities were primarily attributed to the loss of Cav-2, as Cav-1 null mice showed Cav-2 deficiency, but Cav-2 null mice had normal Cav-1 levels.
- Cav-1 and Cav-2 were not expressed in mature skeletal myofibers, suggesting abnormalities originate in stem/precursor cells.
- Skeletal muscle from Cav-3(-/-) mice showed no such abnormalities.
Conclusions:
- Caveolin-2 deficiency is responsible for age-related skeletal muscle abnormalities, including tubular aggregates.
- Cav-2(-/-) mice provide a novel, genetically defined model for studying the pathogenesis of tubular aggregate formation.
- The genesis of these muscle defects is linked to stem/precursor cells, such as satellite cells or myoblasts, rather than mature myofibers.
