NDRGl cell protein Type 4D research - from Japan

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Research from Mol Cell Biol. 2004 May;24(9):3949-56. Related Articles,

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Ndrg1-deficient mice exhibit a progressive demyelinating disorder of

peripheral nerves.

Okuda T, Higashi Y, Kokame K, Tanaka C, Kondoh H, Miyata T.

National Cardiovascular Center Research Institute, Suita, Osaka

565-8565, Japan.

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.