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-1alpha 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.