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 β-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9689-9694 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 97 |
| Issue number | 17 |
| State | Published - Aug 15 2000 |
Fingerprint
ASJC Scopus subject areas
- Genetics
- General
Cite this
Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype. / Galbiati, Ferruccio; Volonté, Daniela; Chu, Jeffrey B.; Li, Maomi; Fine, Samson W.; Fu, Maofu; Bermudez, Jorge; Pedemonte, Marina; Weidenheim, Karen M.; Pestell, Richard G.; Minetti, Carlo; Lisanti, Michael P.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 17, 15.08.2000, p. 9689-9694.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype
AU - Galbiati, Ferruccio
AU - Volonté, Daniela
AU - Chu, Jeffrey B.
AU - Li, Maomi
AU - Fine, Samson W.
AU - Fu, Maofu
AU - Bermudez, Jorge
AU - Pedemonte, Marina
AU - Weidenheim, Karen M.
AU - Pestell, Richard G.
AU - Minetti, Carlo
AU - Lisanti, Michael P.
PY - 2000/8/15
Y1 - 2000/8/15
N2 - 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 β-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.
AB - 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 β-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.
UR - http://www.scopus.com/inward/record.url?scp=12944317278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12944317278&partnerID=8YFLogxK
M3 - Article
C2 - 10931944
AN - SCOPUS:12944317278
VL - 97
SP - 9689
EP - 9694
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 17
ER -