Distinct Effects of Contraction-Induced InjuryIn Vivoon Four Different Murine Models of Dysferlinopathy

[摘要] Mutations in theDYSFgene, encoding dysferlin, cause muscular dystrophies in man.We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysfim/AwaJ (B10.SJL), and A/J and B6.A-Dysfprmd/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 DMDmdxmice 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.

[学科分类] 基础医学