Defective brain development in mice lacking the Hif-1alpha gene in neural cells.
Defective brain development in mice lacking the Hif-1alpha gene in neural cells.
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发表时间：
2003
影响因子：
5.3
通讯作者：
S. Tomita;M. Ueno;M. Sakamoto;Yuki Kitahama;M. Ueki;N. Maekawa;H. Sakamoto;M. Gassmann;R. Kageyama;Natsuo Ueda;F. Gonzalez;Y. Takahama
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文献类型：
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作者：
S. Tomita;M. Ueno;M. Sakamoto;Yuki Kitahama;M. Ueki;N. Maekawa;H. Sakamoto;M. Gassmann;R. Kageyama;Natsuo Ueda;F. Gonzalez;Y. Takahama
缺氧诱导因子 1α (HIF-1α) 对于胚胎发生和发病过程中的血管发育至关重要。然而，人们对其在大脑发育中的作用知之甚少。为了研究 HIF-1α 在中枢神经系统中的功能，我们使用具有巢蛋白启动子驱动的 Cre 的 Cre/LoxP 系统制作了条件敲除小鼠。神经细胞特异性 HIF-1α 缺陷小鼠表现出脑积水，并伴有神经细胞减少和空间记忆受损。神经细胞的凋亡与突变胚胎端脑的血管退化同时发生，这些胚胎缺陷通过体内 HIF-1α 基因传递到胚胎而成功恢复。这些结果表明，神经细胞中 HIF-1α 的表达对于大脑的正常发育至关重要，并建立了一种小鼠模型，该模型可用于评估缺血（包括缺氧介导的脑积水）的治疗策略。
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.