DNM2 levels normalization improves muscle phenotypes of a novel mouse model for moderate centronuclear myopathy.

ABSTRACT: Dynamin 2 (DNM2) is a ubiquitously expressed GTPase regulating membrane trafficking and cytoskeleton dynamics. Heterozygous dominant mutations in DNM2 cause centronuclear myopathy (CNM), associated with muscle weakness and atrophy and histopathological hallmarks as fiber hypotrophy and organelles mis-position. Different severities range from the severe neonatal onset form to the moderate form with childhood onset and to the mild adult onset form. No therapy is approved for CNM. Here we aimed to validate and rescue a mouse model for the moderate form of DNM2-CNM harboring the common DNM2 R369W missense mutation. Dnm2^R369W/+ mice presented with increased DNM2 protein level in muscle and moderate CNM-like phenotypes with force deficit, muscle and fiber h

SUBMITTER: de Carvalho Neves J 

PROVIDER: S-EPMC10400865 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature