title: A new model of experimental fibrosis in hindlimb skeletal muscle of adult mdx mouse mimicking muscular dystrophy.
abstract: BACKGROUND
  Duchenne Muscular Dystrophy (DMD) is characterized by the lack of dystrophin that leads to severe myofiber degeneration. We have shown that endomysial fibrosis is correlated with age at ambulation loss in DMD patients. However, the dystrophin-deficient mdx mouse does not have fibrotic lesions in adult limb muscles. Here, we describe a model of chronic mechanical muscle injury that triggers chronic lesions in mdx hindlimb muscle.
  
  
  METHODS
  Micromechanical injuries were performed daily in tibialis anterior muscles for 2 weeks.
  
  
  RESULTS
  Endomysial fibrosis appeared beginning 1 week post-injury, remained stable for 3 months and was associated with loss of specific maximal force. Fibrosis was associated with an increased expression of factors involved in fibrogenesis including α-smooth muscle actin, connective tissue growth factor, and lysyl oxidase, which colocalized with collagen deposits.
  
  
  CONCLUSIONS
  This induced fibrotic dystrophic model may be useful to study mechanisms of fibrosis in dystrophinopathies and to evaluate antifibrotic treatments.
authors.affiliation: Inserm, U1016, Institut Cochin-Département Génétique et Développement, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Ludovic
authors.initials: L
authors.lastname: Arnold
authors.forename: Alban
authors.initials: A
authors.lastname: Vignaud
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cuvellier
authors.forename: Houda
authors.initials: H
authors.lastname: Yacoub-Youssef
authors.forename: Romain K
authors.initials: RK
authors.lastname: Gherardi
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chretien
authors.forename: Rémi
authors.initials: R
authors.lastname: Mounier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D006614:Hindlimb; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism
chemical_list: D000199:Actins; D015415:Biomarkers; D016189:Dystrophin; C544013:alpha-smooth muscle actin, mouse; D055513:Connective Tissue Growth Factor; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase