Expression profiling in stably regenerating skeletal muscle of dystrophin-deficient mdx mice.
The mdx mouse is comparable to Duchenne muscular dystrophy in having an absence of dystrophin. While dystrophic human skeletal muscle undergoes progressive degeneration, in the mdx mouse regeneration and tissue remodeling substantially compensate for the lack of dystrophin. To better understand the molecular events leading to active muscle regeneration in mdx muscles, we have determined the gene expression profiles of wild-type and mdx hind limb muscles using oligonucleotide arrays. Compared to wild-type, 58 genes were found to be differentially expressed in mdx. The molecular signature of actively regenerating skeletal muscle in young adult mdx mice showed upregulation of muscle development genes and genes involved in immune response, proteolysis and extracellular matrix remodeling. Moreover, energy metabolism and mitochondrial function were not compromised. Insights into the processes activated in the mdx muscle to compensate for chronic degeneration may have important implications for therapy in patients with muscular dystrophy.
Boer
Judith M
JM
Department of Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands. j.m.boer@lumc.nl
de Meijer
Emile J
EJ
Mank
Eveline M
EM
van Ommen
Gertjan B
GB
den Dunnen
Johan T
JT
D000818:Animals; D016189:Dystrophin / Q000172:deficiency*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D015854:Up-Regulation
D016189:Dystrophin