Myopathy reversion in mice after restauration of mitochondrial complex I

ABSTRACT: Myopathies are common manifestations of mitochondrial diseases. To investigate whether gene replacement can be used as an effective strategy to treat or cure mitochondrial myopathies, we have generated a complex I conditional knockout mouse model lacking NDUFS3 subunit in skeletal muscle. NDUFS3 protein levels were undetectable in muscle of 15 days old smKO mice, and myopathy symptoms could be detected by 2 months of age, worsening over time. rAAV9-Ndufs3 delivered systemically into 15-18 days old mice effectively restored NDUFS3 levels in skeletal muscle, precluding the development of the myopathy. To test the ability of rAAV9-mediated gene replacement to revert muscle function after onset, we also treated post-symptomatic, 2-month-old mice. The injected mice showed a remarkable improveme

SUBMITTER: Claudia Pereira 

PROVIDER: S-SCDT-EMM-2019-10674 | biostudies-other |

REPOSITORIES: biostudies-other