CMT 4D: Differential expression patterns of NDRG family proteins in the CNS

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J Histochem Cytochem. 2008 Feb;56(2):175-82.

Differential expression patterns of NDRG family proteins in the

central nervous system.

Okuda T, Kokame K, Miyata T.

National Cardiovascular Center Research Institute, 5-7-1

Fujishirodai, Suita, Osaka 565-8565, Japan.

The N-myc downstream-regulated gene (NDRG) family consists of four

proteins: NDRG1, NDRG2, NDRG3, and NDRG4 in mammals. NDRG1 has been

thoroughly studied as an intracellular protein associated with stress

response, cell growth, and differentiation. A nonsense mutation in

the NDRG1 gene causes hereditary motor and sensory neuropathy,

Charcot-Marie-Tooth disease type 4D.

We previously generated Ndrg1-deficient mice and found that they

exhibited peripheral nerve degeneration caused by severe

demyelination, but that the complicated motor abilities were

retained. These results implied that other NDRG family proteins may

compensate for the NDRG1 deficiency in the central nervous system.

In this study we raised specific antibodies against each member of

the NDRG protein family and examined their cellular expression

patterns in the mouse brain. In the cerebrum, NDRG1 and NDRG2 were

localized in oligodendrocytes and astrocytes, respectively, whereas

NDRG3 and NDRG4 were ubiquitous. In the cerebellum, NDRG1 and NDRG4

were localized in Purkinje cells and NDRG2 in Bergmann glial cells.

NDRG3 was detected in the nuclei in most cells.

These expression patterns demonstrated the cell type-specific and

ubiquitous localization of the NDRG family proteins. Each NDRG may

play a partially redundant role in specific cells in the brain.