NDRG1 is an intracellular protein that is induced under a number of stress and 
pathological conditions, and it is thought to be associated with cell growth and 
differentiation. Recently, human NDRG1 was identified as a gene responsible for 
hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth 
disease type 4D), which is characterized by early-onset peripheral neuropathy, 
leading to severe disability in adulthood. In this study, we generated mice 
lacking Ndrg1 to analyze its function and elucidate the pathogenesis of 
Charcot-Marie-Tooth disease type 4D. Histological analysis showed that the 
sciatic nerve of Ndrg1-deficient mice degenerated with demyelination at about 5 
weeks of age. However, myelination of Schwann cells in the sciatic nerve was 
normal for 2 weeks after birth. Ndrg1-deficient mice showed muscle weakness, 
especially in the hind limbs, but complicated motor skills were retained. In 
wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells 
rather than the myelin sheath. These results indicate that NDRG1 deficiency 
leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for 
maintenance of the myelin sheaths in peripheral nerves. These mice will be used 
for future analyses of the mechanisms of myelin maintenance.