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Transgenic Expression of Laminin α1 Chain Does Not Prevent Muscle Disease in the mdx Mouse Model for Duchenne Muscular Dystrophy.

Gawlik, Kinga LU ; Oliveira, Bruno LU and Durbeej-Hjalt, Madeleine LU (2011) In American Journal of Pathology 178(4). p.1728-1737
Abstract
Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder, and one of the most frequently encountered, but one for which there is as yet no treatment. Laminin-111 protein therapy was recently shown to be a promising approach to prevent muscle disease in the mdx mouse model of DMD. The present study demonstrated that transgenic expression of laminin α1 chain in mdx animals, resulting in laminin-111 heterotrimer formation in mdx muscle, does not improve the dystrophic phenotype. The mdx mice overexpressing laminin-111 (mdxLMα1) display features of mdx littermates: dystrophic pattern of muscle biopsy, elevated creatine kinase levels, reduced muscle strength, and decreased sarcolemmal integrity. Increased expression of integrin α7... (More)
Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder, and one of the most frequently encountered, but one for which there is as yet no treatment. Laminin-111 protein therapy was recently shown to be a promising approach to prevent muscle disease in the mdx mouse model of DMD. The present study demonstrated that transgenic expression of laminin α1 chain in mdx animals, resulting in laminin-111 heterotrimer formation in mdx muscle, does not improve the dystrophic phenotype. The mdx mice overexpressing laminin-111 (mdxLMα1) display features of mdx littermates: dystrophic pattern of muscle biopsy, elevated creatine kinase levels, reduced muscle strength, and decreased sarcolemmal integrity. Increased expression of integrin α7 is not beneficial for mdxLMα1 muscle, and components of the dystrophin-glycoprotein complex are not restored at the sarcolemma on laminin-111 overexpression. In summary, further studies are needed to verify the functionality of laminin-111 protein therapy in DMD and to describe the molecular events resulting from this approach. (Less)
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Contribution to journal
publication status
published
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in
American Journal of Pathology
volume
178
issue
4
pages
1728 - 1737
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000298306700030
  • pmid:21435454
  • scopus:79953659758
ISSN
1525-2191
DOI
10.1016/j.ajpath.2010.12.030
language
English
LU publication?
yes
id
c0a6d883-a574-41b1-83b1-55197e94435a (old id 1883461)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21435454?dopt=Abstract
date added to LUP
2011-04-01 21:30:17
date last changed
2017-04-09 03:08:44
@article{c0a6d883-a574-41b1-83b1-55197e94435a,
  abstract     = {Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder, and one of the most frequently encountered, but one for which there is as yet no treatment. Laminin-111 protein therapy was recently shown to be a promising approach to prevent muscle disease in the mdx mouse model of DMD. The present study demonstrated that transgenic expression of laminin α1 chain in mdx animals, resulting in laminin-111 heterotrimer formation in mdx muscle, does not improve the dystrophic phenotype. The mdx mice overexpressing laminin-111 (mdxLMα1) display features of mdx littermates: dystrophic pattern of muscle biopsy, elevated creatine kinase levels, reduced muscle strength, and decreased sarcolemmal integrity. Increased expression of integrin α7 is not beneficial for mdxLMα1 muscle, and components of the dystrophin-glycoprotein complex are not restored at the sarcolemma on laminin-111 overexpression. In summary, further studies are needed to verify the functionality of laminin-111 protein therapy in DMD and to describe the molecular events resulting from this approach.},
  author       = {Gawlik, Kinga and Oliveira, Bruno and Durbeej-Hjalt, Madeleine},
  issn         = {1525-2191},
  language     = {eng},
  number       = {4},
  pages        = {1728--1737},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Transgenic Expression of Laminin α1 Chain Does Not Prevent Muscle Disease in the mdx Mouse Model for Duchenne Muscular Dystrophy.},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2010.12.030},
  volume       = {178},
  year         = {2011},
}