title: Dystrophin-dependent muscle degeneration requires a fully functional contractile machinery to occur in C. elegans.
abstract: In mammals, the lack of dystrophin leads to a degeneration of skeletal muscles. It has been known for many years that this pathology can be blocked by denervation or immobilization of muscles. It is not yet clear, however, whether this suppressing effect is due to the absence of fiber contraction per se, or to other mechanisms which may be induced by such treatments. We took advantage of the genetic tools available in the animal model Caenorhabditis elegans to address this question. Using RNA interference and existing mutants, we genetically impaired the excitation-contraction cascade at specific points in a dystrophin-deficient C. elegans strain which normally undergoes extensive muscle degeneration. Our data show that reducing sarcomere contraction by slightly impairing the contraction machinery is sufficient to dramatically suppress muscle degeneration. Thus, it is the physical tension exerted on the muscle fibers which is the key deleterious event in the absence of dystrophin.
authors.affiliation: CGMC, CNRS-UMR 5534, Université Claude Bernard Lyon-1, 69622 Villeurbanne Cedex, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mariol
authors.forename: Edwige
authors.initials: E
authors.lastname: Martin
authors.forename: Lucie
authors.initials: L
authors.lastname: Chambonnier
authors.forename: Laurent
authors.initials: L
authors.lastname: Ségalat
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000235:genetics; D009121:Muscle Denervation / Q000379:methods; D009124:Muscle Proteins; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded / Q000627:therapeutic use; D014157:Transcription Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D016189:Dystrophin; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded; D014157:Transcription Factors; C406103:dys-1 protein, C elegans; C066645:HLH-1 protein, C elegans