Lights on for low oxygen: a noninvasive mouse model useful for sensing oxygen deficiency

In vitro experimentation is valuable as a precursor to in vivo research; however, as we all know too well, not every in vitro finding leads to confirmation in vivo. In fact, conflicting results often occur because in vitro experiments lack all the necessary factors that impinge upon normal physiology in live animals. We are fortunate when in vivo models can be created that allow for direct observation of pharmacological effects. Kaelin and colleagues have created a mouse line that expresses the oxygen-dependent degradation domain (ODD) of hypoxia-induced factor-1alpha (HIF-1alpha) fused to the common firefly luciferase gene, under the control of a promoter that ensures organism-wide expression. In conditions of normoxia, the protein is quickly degraded, but in hypoxic situations, the protein is not degraded and administration of substrate illuminates the areas of expression. This technique allows for the observation of the effects of agents on oxygen tension in particular organs. Implicit is the adaptability of this model, wherein other promoters (e.g., tissue-specific) can be utilized or other disease models can be studied.