Defective brain development in mice lacking the Hif-1α gene in neural cells
Defective brain development in mice lacking the Hif-1α gene in neural cells
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DOI：
10.1128/mcb.23.19.6739-6749.2003
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发表时间：
2003-10-01
影响因子：
5.3
通讯作者：
Takahama, Y
中科院分区：
文献类型：
--
作者：
Tomita, S;Ueno, M;Takahama, Y
缺氧诱导因子1 α（HIF-1 alpha）是胚胎发育过程中血管发育所必需的。然而，人们对它在大脑发育中的作用知之甚少。为了研究HIF-1 α在中枢神经系统中的功能，用具有巢蛋白启动子驱动的Cre的Cre/LoxP系统制备条件性敲除小鼠。神经细胞特异性HIF-1 α缺陷小鼠表现出脑积水，伴有神经细胞减少和空间记忆障碍。神经细胞的凋亡与突变胚胎端脑中的血管退化相一致，并且通过将HIF-1 α体内基因递送至胚胎成功地恢复了这些胚胎缺陷。这些结果表明，HIF-1 α在神经细胞中的表达对于大脑的正常发育是必不可少的，并建立了一个小鼠模型，该模型可用于评估缺血的治疗策略，包括缺氧介导的脑积水。
Hypoxia-inducible factor 1alpha (HIF-1alpha) is essential for vascular development during embryogenesis and pathogenesis. However, little is known about its role in brain development. To investigate the function of HIF-1alpha in the central nervous system, a conditional knockout mouse was made with the Cre/LoxP system with a nestin promoter-driven Cre. Neural cell-specific HIF-1alpha-deficient mice exhibit hydrocephalus accompanied by a reduction in neural cells and an impairment of spatial memory. Apoptosis of neural cells coincided with vascular regression in the telencephalon of mutant embryos, and these embryonic defects were successfully restored by in vivo gene delivery of HIF-1alpha to the embryos. These results showed that expression of HIF-1alpha in neural cells was essential for normal development of the brain and established a mouse model that would be useful for the evaluation of therapeutic strategies for ischemia, including hypoxia-mediated hydrocephalus.