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Generation of a hypoxia‐sensing mouse model
genesis ( IF 2.4 ) Pub Date : 2019-12-24 , DOI: 10.1002/dvg.23352
Qun Lin 1 , Yan Huang 2 , Frank J Giordano 2 , Zhong Yun 1
Affiliation  

Oxygen (O2) homeostasis is essential to the metazoan life. O2‐sensing or hypoxia‐regulated molecular pathways are intimately involved in a wide range of critical cellular functions and cell survival from embryogenesis to adulthood. In this report, we have designed an innovative hypoxia sensor (O2CreER) based on the O2‐dependent degradation domain of the hypoxia‐inducible factor‐1α and Cre recombinase. We have further generated a hypoxia‐sensing mouse model, R26‐O2CreER, by targeted insertion of the O2CreER‐coding cassette in the ROSA26 locus. Using the ROSAmTmG mouse strain as a reporter, we have found that this novel hypoxia‐sensing mouse model can specifically identify hypoxic cells under the pathological condition of hind‐limb ischemia in adult mice. This model can also label embryonic cells including vibrissal follicle cells in E13.5–E15.5 embryos. This novel mouse model offers a valuable genetic tool for the study of hypoxia and O2 sensing in mammalian systems under both physiological and pathological conditions.

中文翻译:

缺氧感应小鼠模型的生成

氧气(O 2)稳态对后生生活至关重要。从胚胎发生到成年,O 2感应或缺氧调节的分子途径与广泛的关键细胞功能和细胞存活密切相关。在本报告中,我们基于低氧诱导因子-1α和Cre重组酶的O 2依赖性降解域设计了一种创新的低氧传感器(O 2 CreER)。通过将O 2 CreER编码盒有针对性地插入ROSA26基因座,我们进一步生成了一个低氧敏感性小鼠模型R26-O 2 CreER 。使用ROSA mTmG作为记者的小鼠品系,我们发现这种新型的低氧敏感小鼠模型可以在成年小鼠后肢缺血的病理条件下特异性鉴定低氧细胞。该模型还可以标记E13.5–E15.5胚胎中的胚细胞,包括纤毛滤泡细胞。这种新颖的小鼠模型为在生理和病理条件下研究哺乳动物系统中的缺氧和O 2传感提供了有价值的遗传工具。
更新日期:2019-12-24
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