Skip Navigation



Human Molecular Genetics Advance Access published online on March 9, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi095
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
14/8/1029    most recent
ddi095v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Dominov, J. A.
Right arrow Articles by Miller, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dominov, J. A.
Right arrow Articles by Miller, J. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved

Article

Muscle-specific BCL2 expression ameliorates muscle disease in laminin {alpha}2-deficient, but not dystrophin-deficient, mice

Janice A. Dominov 1*, Amanda J. Kravetz 2, Magdalena Ardelt 2, Christine A. Kostek 2, Mary Lou Beermann 2, and Jeffrey B. Miller 1

1 Boston Biomedical Research Institute, 64 Grove Street, Watertown MA 02472; Department of Neurology, Harvard Medical School, Boston, MA 02115
2 Boston Biomedical Research Institute, 64 Grove Street, Watertown MA 02472

* To whom correspondence should be addressed.
Janice A. Dominov, E-mail: Dominov{at}bbri.org


  Abstract

To examine the role of apoptosis in neuromuscular disease progression, we have determined if pathogenesis in dystrophin-deficient (mdx) and laminin {alpha}2-deficient (Lama2-null) mice is ameliorated by overexpression of the anti-apoptosis protein BCL2 in diseased muscles. The mdx mice are a model for the human disease, Duchenne Muscular Dystrophy (DMD), and the Lama2-null mice are a model for human Congenital Muscular Dystrophy Type 1A (MDC1A). For these studies, we generated transgenic mice that overexpressed human BCL2 under control of muscle-specific MyoD or MRF4 promoter fragments. We then used cross-breeding to introduce the transgenes into diseased mdx or Lama2-null mice. In mdx mice, we found that overexpression of BCL2 failed to produce any significant differences in muscle pathology. In the Lama2-null mice, in contrast, we found that muscle-specific expression of BCL2 led to a several-fold increase in lifespan and an increased growth rate. Thus, BCL2-mediated apoptosis appears to play a significant role in pathogenesis in laminin {alpha}2-deficiency, but not dystrophin-deficiency, suggesting that therapies designed to ameliorate disease by inhibition of apoptosis are more likely to succeed in MDC1A than in DMD.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
V. K. Vishnudas and J. B. Miller
Ku70 regulates Bax-mediated pathogenesis in laminin-{alpha}2-deficient human muscle cells and mouse models of congenital muscular dystrophy
Hum. Mol. Genet., December 1, 2009; 18(23): 4467 - 4477.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. Xu, S. DeVries, M. Camboni, and P. T. Martin
Overexpression of Galgt2 Reduces Dystrophic Pathology in the Skeletal Muscles of Alpha Sarcoglycan-Deficient Mice
Am. J. Pathol., July 1, 2009; 175(1): 235 - 247.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. E. Davies, S. Sarkar, and D. C. Rubinsztein
Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation
Hum. Mol. Genet., April 15, 2008; 17(8): 1097 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. Xu, K. Chandrasekharan, J. H. Yoon, M. Camboni, and P. T. Martin
Overexpression of the Cytotoxic T Cell (CT) Carbohydrate Inhibits Muscular Dystrophy in the dyW Mouse Model of Congenital Muscular Dystrophy 1A
Am. J. Pathol., July 1, 2007; 171(1): 181 - 199.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. E. Hall, R. J. Bryson-Richardson, S. Berger, A. S. Jacoby, N. J. Cole, G. E. Hollway, J. Berger, and P. D. Currie
The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin {alpha}2-deficient congenital muscular dystrophy
PNAS, April 24, 2007; 104(17): 7092 - 7097.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Meinen, P. Barzaghi, S. Lin, H. Lochmuller, and M. A. Ruegg
Linker molecules between laminins and dystroglycan ameliorate laminin-{alpha}2-deficient muscular dystrophy at all disease stages
J. Cell Biol., March 26, 2007; 176(7): 979 - 993.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. Hnia, G. Hugon, F. Rivier, A. Masmoudi, J. Mercier, and D. Mornet
Modulation of p38 Mitogen-Activated Protein Kinase Cascade and Metalloproteinase Activity in Diaphragm Muscle in Response to Free Radical Scavenger Administration in Dystrophin-Deficient Mdx Mice
Am. J. Pathol., February 1, 2007; 170(2): 633 - 643.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Homma, M. Iwasaki, G. D. Shelton, E. Engvall, J. C. Reed, and S. Takayama
BAG3 Deficiency Results in Fulminant Myopathy and Early Lethality
Am. J. Pathol., September 1, 2006; 169(3): 761 - 773.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.