Mutations in dynamin 2 (DNM2) lead to dominant intermediate Charcot-Marie-Tooth 
neuropathy type B, while a different set of DNM2 mutations cause autosomal 
dominant centronuclear myopathy. In this study, we aimed to elucidate the 
disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type 
B and to find explanations for the tissue-specific defects that are associated 
with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth 
neuropathy type B versus autosomal dominant centronuclear myopathy. We used 
tissue derived from Dnm2-deficient mice to establish an appropriate peripheral 
nerve model and found that dominant intermediate Charcot-Marie-Tooth neuropathy 
type B-associated dynamin 2 mutants, but not autosomal dominant centronuclear 
myopathy mutants, impaired myelination. In contrast to autosomal dominant 
centronuclear myopathy mutants, Schwann cells and neurons from the peripheral 
nervous system expressing dominant intermediate Charcot-Marie-Tooth neuropathy 
mutants showed defects in clathrin-mediated endocytosis. We demonstrate that, as 
a consequence, protein surface levels are altered in Schwann cells. Furthermore, 
we discovered that myelination is strictly dependent on Dnm2 and 
clathrin-mediated endocytosis function. Thus, we propose that altered 
endocytosis is a major contributing factor to the disease mechanisms in dominant 
intermediate Charcot-Marie-Tooth neuropathy type B.