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PMID: 10931944 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 ·2000-08-15 ·Pages 9689-94

Galbiati F, Volonte D, Chu JB, Li M, Fine SW, Fu M, Bermudez J, Pedemonte M, Weidenheim KM, Pestell RG, Minetti C, Lisanti MP

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 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.

MeSH Terms
Animals Caveolin 3 Caveolins Cell Nucleus/pathology Creatine Kinase/blood Cytoskeletal Proteins/metabolism Disease Models, Animal Down-Regulation Dystroglycans Dystrophin/metabolism Female Hindlimb/physiopathology Immunohistochemistry Male Membrane Glycoproteins/metabolism Membrane Proteins/genetics,metabolism,ultrastructure Mice Mice, Inbred mdx Mice, Transgenic Microscopy, Electron Muscle Fibers, Skeletal/metabolism,pathology,physiology Muscle, Skeletal/metabolism,pathology,physiopathology Muscular Dystrophy, Duchenne/genetics,metabolism,pathology,physiopathology Necrosis Phenotype Rotation Sarcolemma/pathology Transgenes/genetics
Chemicals
Cav3 protein, mouse Caveolin 3 Caveolins Cytoskeletal Proteins Dystrophin Membrane Glycoproteins Membrane Proteins Dystroglycans Creatine Kinase
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Galbiati F
Departments of Molecular Pharmacology, Pathology, Developmental and Molecular Biology, and Neuropathology and Pathology, and The Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Volonte 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
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.160249097
Published
2000-08-15
Pages
9689-94
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16926
Subset
IM
Grants
Telethon · 1111 · Italy
NIAMS NIH HHS · R01 AR046792 · United States
NIAMS NIH HHS · R01 AR-46792 · United States
External Links
PubMed source DOI: 10.1073/pnas.160249097 PMC Full Text View journal details
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