Journal Article

Muscle-specific BCL2 expression ameliorates muscle disease in laminin α2-deficient, but not in dystrophin-deficient, mice

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

in Human Molecular Genetics

Volume 14, issue 8, pages 1029-1040
Published in print April 2005 | ISSN: 0964-6906
Published online March 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi095
Muscle-specific BCL2 expression ameliorates muscle disease in laminin α2-deficient, but not in dystrophin-deficient, mice

Show Summary Details

Preview

To examine the role of apoptosis in neuromuscular disease progression, we have determined whether pathogenesis in dystrophin-deficient (mdx) and laminin α2-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 contrast, in the Lama2-null mice, 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 of laminin α2 deficiency, but not of dystrophin deficiency, suggesting that therapies designed to ameliorate disease by inhibition of apoptosis are more likely to succeed in MDC1A than in DMD.

Journal Article.  8690 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.