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Am J Physiol Cell Physiol (April 24, 2002). doi:10.1152/ajpcell.00112.2002
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Articles in PresS, published online ahead of print April 24, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00112.2002
Submitted on March 12, 2002
Accepted on April 17, 2002

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

Karl Rouger1, Karl Rouger2, Martine Le Cunff1, Martine Le Cunff2, Marja Steenman1, Marja Steenman2, Marie-Claude Potier3, Marie-Claude Potier3, Nathalie Gibelin3, Nathalie Gibelin3, Claude A Dechesne4, Claude A Dechesne4, Jean J Leger1*, and Jean J Léger2

1 Faculte de Medecine, INSERM U533, Nantes, France
2 Faculté de Médecine, INSERM U533, Nantes, France
3 ESPCI, CNRS UMR7637, Paris, France
4 CNRS UMR6548, Nice, France

* To whom correspondence should be addressed. E-mail: jean.leger{at}nantes.inserm.fr.

Mdx is a mouse model for human Duchenne muscular dystrophy (DMD), an X-linked degenerative disease of skeletal muscle tissue characterized by the absence of the dystrophin protein. Mdx mice display a much milder phenotype than DMD patients. After the first weeks 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 1082 genes, previously selected by a subtractive method, in control and mdx, hindlimb and diaphragm muscles at twelve time-points over the first year of the mouse life. We determined that (a) the dystrophin gene defect induced marked expression remodeling of 112 genes encoding proteins implicated in diverse muscle cell functions, and (b) 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.




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