Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan.
Int J Mol Sci. 2019 Jul 23;20(14):3596. doi: 10.3390/ijms20143596.
WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (). Immunostaining revealed that Wwox is expressed in neurons, astrocytes, and oligodendrocytes. cortices were characterized by a reduction in neurite growth without a reduced number of neurons, severe reduction in myelination with a reduced number of mature oligodendrocytes, and a reduction in cell populations of astrocytes and microglia. These results indicate that Wwox is essential for normal development of neurons and glial cells in the cerebral cortex.
WW 结构域包含氧化还原酶 (Wwox) 是一种假定的肿瘤抑制因子。已经发现 Wwox 的几种种系突变与以癫痫、生长迟缓以及早逝为特征的婴儿神经发育障碍有关。然而，人们对 Wwox 突变与这些疾病之间的病理联系或 Wwox 在大脑发育中的生理作用知之甚少。在这项研究中，我们研究了 Wwox 在大脑前脑中的年龄相关表达和组织学定位，以及在一种具有癫痫的致死性侏儒症大鼠模型中 Wwox 基因功能丧失突变的影响。免疫染色显示 Wwox 表达于神经元、星形胶质细胞和少突胶质细胞中。与野生型相比，突变体皮质表现为神经突生长减少而神经元数量无减少、髓鞘形成严重减少而成熟少突胶质细胞数量减少、星形胶质细胞和小胶质细胞的细胞群体减少。这些结果表明 Wwox 对于大脑皮质中神经元和神经胶质细胞的正常发育是必需的。
