BIN1 reduction ameliorates DNM2-related Charcot-Marie-Tooth neuropathy.

ABSTRACT: Charcot-Marie-Tooth (CMT) disease, the most common inherited neuromuscular disorder, manifests as progressive muscle weakness and peripheral nerve defects. Dominant mutations in DNM2, encoding the large GTPase dynamin 2, result in CMT without any suggested therapeutic strategy. Different dominant mutations in DNM2 also cause centronuclear myopathy (CNM), and increasing BIN1 (amphiphysin 2), an endogenous modulator of DNM2, rescued CNM in mice. Here, we found that increasing BIN1 level exacerbated the phenotypes of the Dnm2^K562E/+ mouse carrying the most common DNM2-CMT mutation. Conversely, whole-body reduction of Bin1 expression level, through the generation of Dnm2^K562E/+ mice with heterozygous loss of BIN1, restored motor p

SUBMITTER: Goret M 

PROVIDER: S-EPMC11912451 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature