title: Distinct effects of contraction-induced injury in vivo on four different murine models of dysferlinopathy.
abstract: Mutations in the DYSF gene, encoding dysferlin, cause muscular dystrophies in man. We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysf(im)/AwaJ (B10.SJL), and A/J and B6.A-Dysf(prmd)/GeneJ (B6.A/J). The former but not the latter two are overtly myopathic and weaker at 3 months of age. Following repetitive large-strain injury (LSI) caused by lengthening contractions, all except B6.A/J showed ~40% loss in contractile torque. Three days later, torque in SJL/J, B10.SJL and controls, but not A/J, recovered nearly completely. B6.A/J showed ~30% torque loss post-LSI and more variable recovery. Pre-injury, all dysferlinopathic strains had more centrally nucleated fibers (CNFs) and all but A/J showed more inflammation than controls. At D3, all dysferlinopathic strains showed increased necrosis and inflammation, but not more CNFs; controls were unchanged. Dystrophin-null DMD(mdx) mice showed more necrosis and inflammation than all dysferlin-nulls. Torque loss and inflammation on D3 across all strains were linearly related to necrosis. Our results suggest that (1) dysferlin is not required for functional recovery 3 days after LSI; (2) B6.A/J mice recover from LSI erratically; (3) SJL/J and B10.SJL muscles recover rapidly, perhaps due to ongoing myopathy; (4) although they recover function to different levels, all 4 dysferlinopathic strains show increased inflammation and necrosis 3 days after LSI.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Roche
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Ru
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bloch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000073939:Dysferlin; D006651:Histocytochemistry; D007249:Inflammation; D008264:Macrophages / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries* / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000473:pathology*; D009336:Necrosis; D019415:Torque
chemical_list: C497505:Dysf protein, mouse; D000073939:Dysferlin; D008565:Membrane Proteins