Ishihara Keiichi
Department of Pathological Biochemistry, Kyoto Pharmaceutical University.
Yakugaku Zasshi. 2021;141(3):369-373. doi: 10.1248/yakushi.20-00198-5.
Developmental retardation of the brain with reduced cortical neurogenesis is observed in Ts1Cje mice, a model of Down syndrome (DS) as it is in people with DS; however, the mechanisms and the responsible gene(s) remain unknown. The goal of the present study is to establish a therapeutic approach for treating the delayed brain development in DS. To achieve this, we have utilized multiple OMICS analyses, including proteomics and transcriptomics, to uncover the molecular alterations in the brains of DS model mice. Furthermore, we have elucidated that a transcriptional factor, the Erg gene, which is coded in the trisomic region, contributed to reduced cortical neurogenesis in the embryo of a DS mouse model by a molecular genetic technique, the "in vivo gene subtraction method". In the current review, I will introduce our recent work, the identification of the gene responsible for delayed brain development in the DS mouse model and will discuss the possibility that blood vessel dysfunction may be associated with reduced embryonic neurogenesis in DS.
在唐氏综合征(DS)模型小鼠Ts1Cje中观察到大脑发育迟缓,皮质神经发生减少,就像DS患者一样;然而,其机制和相关基因仍不清楚。本研究的目的是建立一种治疗DS中脑发育延迟的方法。为了实现这一目标,我们利用了多种组学分析,包括蛋白质组学和转录组学,来揭示DS模型小鼠大脑中的分子变化。此外,我们通过分子遗传学技术“体内基因减法”阐明,位于三体区域的转录因子Erg基因导致DS小鼠模型胚胎中的皮质神经发生减少。在当前的综述中,我将介绍我们最近的工作,即鉴定DS小鼠模型中导致脑发育延迟的基因,并将讨论血管功能障碍可能与DS中胚胎神经发生减少相关的可能性。