Mice with muscle-specific deletion of Bin1 recapitulate centronuclear myopathy and acute downregulation of dynamin 2 improves their phenotypes.

ABSTRACT: Mutations in the BIN1 (Bridging Interactor 1) gene, encoding the membrane remodeling protein amphiphysin 2, cause centronuclear myopathy (CNM) associated with severe muscle weakness and myofiber disorganization and hypotrophy. There is no available therapy, and the validation of therapeutic proof of concept is impaired by the lack of a faithful and easy-to-handle mammalian model. Here, we generated and characterized the Bin1^mck-/- mouse through Bin1 knockout in skeletal muscle. Bin1^mck-/- mice were viable, unlike the constitutive Bin1 knockout, and displayed decreased muscle force and most histological hallmarks of CNM, including myofiber hypotrophy and intracellular disorganization. Notably, Bin1^mck-/- myofibers presented strong defects in mitochondria and

SUBMITTER: Silva-Rojas R 

PROVIDER: S-EPMC8821932 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature