Generation of a hypoxia-sensing mouse model

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 (O₂ CreER) 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-O₂ CreER, by targeted insertion of the O₂ CreER-coding cassette in the ROSA26 locus. Using the ROSA^mTmG 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.