Measuring in vivo responses to endogenous and exogenous oxidative stress using a novel Heme Oxygenase 1 reporter mouse

Abstract

Hmox1 protein holds great promise as a biomarker of in vivo stress responses as it is highly induced in stressed or damaged cells. However, Hmox1 expression patterns have thus far only been available in simple model organisms with limited relevance to humans. We now report a new Hmox1 reporter line that makes it possible to obtain this information in mice, a premiere model system for studying human disease and toxicology. Using a state-of-the-art strategy, we expressed multiple complementary reporter molecules from the murine Hmox1 locus, including firefly luciferase to allow long-term, non-invasive imaging of Hmox1 expression, and β-galactosidase for high-resolution mapping of expression patterns post-mortem. We validated the model by confirming the fidelity of reporter expression, and its responsiveness to oxidative and inflammatory stimuli. In addition to providing blueprints for Hmox1 expression in mice that provide novel biological insights, this work paves the way for the broad application of this model to establish cellular stresses induced by endogenous processes and those resulting from exposure to drugs and environmental agents. It will also enable studies on the role of oxidative stress in the pathogenesis of disease and its prevention.

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