BIN1 modulation in vivo rescues dynamin-related myopathy.

ABSTRACT: The mechanoenzyme dynamin 2 (DNM2) is crucial for intracellular organization and trafficking. DNM2 is mutated in dominant centronuclear myopathy (DNM2-CNM), a muscle disease characterized by defects in organelle positioning in myofibers. It remains unclear how the in vivo functions of DNM2 are regulated in muscle. Moreover, there is no therapy for DNM2-CNM to date. Here, we overexpressed human amphiphysin 2 (BIN1), a membrane remodeling protein mutated in other CNM forms, in Dnm2^RW/+ and Dnm2^RW/RW mice modeling mild and severe DNM2-CNM, through transgenesis or with adeno-associated virus (AAV). Increasing BIN1 improved muscle atrophy and main histopathological features of Dnm2^RW/+ mice and rescued the perinatal lethality and surv

SUBMITTER: Lionello VM 

PROVIDER: S-EPMC8892365 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature