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在缺乏蛋白质ARNT的小鼠中,异常血管生成和对葡萄糖和氧气缺乏的反应
E Maltepe1, J V Schmidt, D Baunoch
1Department of Pathology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA.
Nature
|March 27, 1997
概括
阿里碳受体核转位器 (ARNT) 对于胚胎发育至关重要,调节对低氧和葡萄糖的反应. 在小鼠中,ARNT 缺乏导致发育失败和缺陷血管形成.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 细胞生理学 细胞生理学
背景情况:
- ARNT是bHLH-PAS家族中的转录因子,与AHR和HIF-1alpha形成异构体.
- ARNT-AHR调节了异生菌的新陈代谢,而ARNT-HIF-1alpha则参与了缺氧反应.
研究的目的:
- 研究ARNT在胚胎发育和细胞反应中的作用.
- 阐明ARNT在低氧和低血糖信号通路中的功能.
主要方法:
- 在小鼠胚胎干细胞 (ES) 中对Arnt位点的有针对性的破坏.
- 在低氧和低血糖条件下分析Arnt-/- ES细胞中的基因激活.
- 对Arnt-/-胚胎的表型分析.
主要成果:
- Arnt-/- ES细胞在低氧张力和降低葡萄糖的反应中未能激活基因.
- Arnt-/-胚胎表现出胚胎死亡率在过去的10.5.5天.
- 在Arnt-/-胚胎中观察到有缺陷的黄囊和分支弧血管生成,发育迟缓和胚胎消耗.
结论:
- ARNT对于胚胎活力至关重要,调节对低氧和低血糖的反应.
- ARNT在血管生成中起着至关重要的作用,可能通过血管内皮生长因子.
- 提出了一个模型,其中ARNT激活在器官生成过程中促进血管化.
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