Research on the nerve and endocrine function of the tumor suppressor gene WWOX located in a chromosomal fragile site

WWOX编码基因位于染色体脆性部位，WWOX是抗肿瘤因子的候选基因。WWOX的生理功能仍不清楚。在本研究中，我们利用自发突变导致WWOX功能丧失的LDE/LDE大鼠，研究了WWOX在中枢神经系统中的作用。WWOX在正常大鼠的大脑皮层、海马区、脑干等中枢神经系统及大部分脏器中均有表达。LDE/LDE大鼠大脑和脑干神经元密度和颗粒密度明显低于正常大鼠。在BrdU掺入实验中，LDE/LDE大鼠侧脑室下区BrdU阳性细胞数明显低于正常大鼠。这些结果提示WWOX可能是通过调节神经干细胞的增殖和分化来维持神经元和神经胶质细胞的正常数量所必需的。

The gene encoding WWOX is located in a chromosomal fragile site, and WWOX is a candidate for antitumor factor. The physiological function of WWOX has remained unknown. In the present study, we examined the role of WWOX in central nerve system using lde/lde rats in which a spontaneous mutation causes the loss of WWOX function. The expression of WWOX was detected in most of organs examined and in central nerve system such as cerebral cortex, hippocampus, and brainstem in normal rats. The neuronal and grail densities in cerebrum and brainstem were significantly lower in lde/lde than in normal rats. In the BrdU-incorporation assay, the number of BrdU-positive cells was significantly lower in the subventricular zone of lateral ventricle of lde/lde than that of normal rats. These results suggest that WWOX might be necessary for maintaining normal numbers of neuron and glia through the regulation of proliferation and differentiation in neuronal stem cells.