Okuda Tomohiko, Kokame Koichi, Miyata Toshiyuki
National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
J Histochem Cytochem. 2008 Feb;56(2):175-82. doi: 10.1369/jhc.7A7323.2007. Epub 2007 Nov 12.
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.
N-myc下游调控基因(NDRG)家族在哺乳动物中由四种蛋白质组成:NDRG1、NDRG2、NDRG3和NDRG4。NDRG1作为一种与应激反应、细胞生长和分化相关的细胞内蛋白质,已得到充分研究。NDRG1基因中的无义突变会导致遗传性运动和感觉神经病变,即4D型夏科-马里-图斯病。我们之前培育出了Ndrg1基因敲除小鼠,发现它们表现出由严重脱髓鞘引起的周围神经退化,但复杂的运动能力得以保留。这些结果表明,其他NDRG家族蛋白质可能在中枢神经系统中补偿了NDRG1的缺陷。在本研究中,我们制备了针对NDRG蛋白质家族各成员的特异性抗体,并检测了它们在小鼠大脑中的细胞表达模式。在大脑中,NDRG1和NDRG2分别定位于少突胶质细胞和星形胶质细胞,而NDRG3和NDRG4分布广泛。在小脑中,NDRG1和NDRG4定位于浦肯野细胞,NDRG2定位于伯格曼胶质细胞。在大多数细胞的细胞核中检测到NDRG3。这些表达模式证明了NDRG家族蛋白质在细胞类型上的特异性定位和广泛分布。每个NDRG可能在大脑中的特定细胞中发挥部分冗余作用。