Type 4 D (early onset) protein research - from Japan

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Is it me or do they keep adding diseases to the CMT catagory?

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From Mol Cell Biol. 2004 May;24(9):3949-56.

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. Laboratory of Developmental Biology, Graduate School of

Frontier Bioscience, Osaka University, Suita, Osaka 565-0871, 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.