title: Analyses of the differentiation potential of satellite cells from myoD-/-, mdx, and PMP22 C22 mice.
abstract: BACKGROUND
  Sporadic and sometimes contradictory studies have indicated changes in satellite cell behaviour associated with the progressive nature of human Duchenne muscular dystrophy (DMD). Satellite cell proliferation and number are reportedly altered in DMD and the mdx mouse model. We recently found that satellite cells in MSVski transgenic mice, a muscle hypertrophy model showing progressive muscle degeneration, display a severe ageing-related differentiation defect in vitro. We tested the hypothesis that similar changes contribute to the gradual loss of muscle function with age in mdx and PMP22 mice, a model of human motor and sensory neuropathy type 1A (HMSN1A).
  
  
  METHODS
  Single extensor digitorum longus muscle fibres were cultured from mdx and PMP22 mice and age- and genetic background-matched controls. Mice at several ages were compared with regard to the differentiation of satellite cells, assayed as the proportion of desmin-expressing cells that accumulated sarcomeric myosin heavy chain.
  
  
  RESULTS
  Satellite cells of 2 month, 6 month, and 12 month old mdx mice were capable of differentiating to a similar extent to age-matched wild type control animals in an in vitro proliferation/differentiation model. Strikingly, differentiation efficiency in individual 6 month and 12 month old mdx animals varies to a much higher extent than in age-matched controls, younger mdx animals, or PMP22 mice. In contrast, differentiation of myoblasts from all myoD null mice assayed was severely impaired in this assay system. The defect in satellite cell differentiation that occurs in some mdx animals arises from a delay in differentiation that is not overcome by IGF-1 treatment at any phase of cultivation.
  
  
  CONCLUSIONS
  Overall, a defect in satellite cell differentiation above that arising through normal ageing does not occur in mdx or PMP22 mouse models of human disease. Nonetheless, the impaired differentiation of satellite cells from some mdx animals suggests that additional factors, environmental or epigenetic, may lead to deteriorating muscle repair through poor differentiation of satellite cells in genetically predisposed individuals.
authors.affiliation: Insitute of Pathology, Medical School of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. marion.schuierer@klinik.uni-r.de
authors.forename: Marion M
authors.initials: MM
authors.lastname: Schuierer
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Mann
authors.forename: Heidi
authors.initials: H
authors.lastname: Bildsoe
authors.forename: Clare
authors.initials: C
authors.lastname: Huxley
authors.forename: Simon M
authors.initials: SM
authors.lastname: Hughes
mesh_terms: D000375:Aging; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology*; D009185:Myelin Proteins / Q000235:genetics*; D017570:MyoD Protein / Q000235:genetics*; D027161:Satellite Cells, Perineuronal / Q000473:pathology*; D013997:Time Factors
chemical_list: D009185:Myelin Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C489545:Pmp22 protein, mouse; D007334:Insulin-Like Growth Factor I