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Am J Physiol Cell Physiol 283: C773-C784, 2002. First published April 24, 2002; doi:10.1152/ajpcell.00112.2002
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Vol. 283, Issue 3, C773-C784, September 2002

Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice

Karl Rouger1, Martine Le Cunff1, Marja Steenman1, Marie-Claude Potier2, Nathalie Gibelin2, Claude A. Dechesne3, and Jean J. Leger1

1 Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) 533, Faculté de Médecine, 44093 Nantes; 2 Centre National à la Recherche Scientifique UMR 7637, Ecole Supérieure de Physique et de Chimie Industrielle, 75005 Paris; and 3 Centre National à la Recherche Scientifique UMR 6548, 06108 Nice, France

The mdx mouse is a model for human Duchenne muscular dystrophy (DMD), an X-linked degenerative disease of skeletal muscle tissue characterized by the absence of the dystrophin protein. The mdx mice display a much milder phenotype than DMD patients. After the first week of life when all mdx muscles evolve like muscles of young DMD patients, mdx hindlimb muscles substantially compensate for the lack of dystrophin, whereas mdx diaphragm muscle becomes progressively affected by the disease. We used cDNA microarrays to compare the expression profile of 1,082 genes, previously selected by a subtractive method, in control and mdx hindlimb and diaphragm muscles at 12 time points over the first year of the mouse life. We determined that 1) the dystrophin gene defect induced marked expression remodeling of 112 genes encoding proteins implicated in diverse muscle cell functions and 2) two-thirds of the observed transcriptomal anomalies differed between adult mdx hindlimb and diaphragm muscles. Our results showed that neither mdx diaphram muscle nor mdx hindlimb muscles evolve entirely like the human DMD muscles. This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays.

muscular dystrophy; mdx mice; complementary deoxyribonucleic acid microarray; differential gene expression


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