Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype
Open accessAbstract
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.
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Increased levels of some proteins have been reported to cause myopathic symptoms, as shown in transgenic mouse lines overexpressing caveolin-3 or gamma-sarcoglycan.
“Increased levels of some proteins have been reported to cause myopathic symptoms, as has been shown in work involving transgenic mouse lines that overexpress either caveolin-3 (Galbiati et al. 2000) or g -sarcoglycan (Zhu et al. 2001).”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Galbiati et al. 2000
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- Authors
- Galbiati, F., Volonté, D., Chu, J. B., Li, M., Fine, S. W., Fu, M., Bermudez, J., Pedemonte, M., Weidenheim, K. M., Pestell, R. G., Minetti, C., & Lisanti, M. P.
- Affiliations
- Albert Einstein College of Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-08-08
- Volume
- 97
- Issue
- 17
- Pages
- 9689-9694
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC16926
- OpenAlex
- W2025297482
- Cited by
- 155
- References
- 49
- Citations by year
- 2026: 4 · 2023: 4 · 2022: 5 · 2021: 1 · 2020: 9 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 8 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR-46792, R01AR046792)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- caveolin-3, Duchenne muscular dystrophy, transgenic overexpression, skeletal muscle fibers, dystrophin, beta-dystroglycan, creatine kinase, muscle necrosis, mdx mice, pathogenesis, mouse model
- MeSH terms
- Animals, Cell Nucleus, Creatine Kinase, Cytoskeletal Proteins, Disease Models, Animal, Female, Hindlimb, Immunohistochemistry, Male, Membrane Glycoproteins, Membrane Proteins, Mice, Transgenic, Microscopy, Electron, Necrosis, Phenotype, Rotation, Sarcolemma, Down-Regulation, Dystrophin, Mice, Inbred mdx, Muscle, Skeletal, Muscle Fibers, Skeletal, Transgenes, Muscular Dystrophy, Duchenne, Caveolins, Dystroglycans, Caveolin 3, Mice
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