Bioluminescence imaging ofCyp1a1-luciferase reporter mice demonstrates prolonged activation of the aryl hydrocarbon receptor in the lung

Abstract

AbstractAryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such asCyp1a1. To dynamically visualise AHR activityin vivo,we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenousCyp1a1locus. Exposure of these animals to FICZ, 3-MC or to dietary I3C induced strong bioluminescence signal andCyp1a1expression in many organs including liver, lung and intestine. Longitudinal studies revealed that AHR activity was surprisingly long-lived in the lung, with sustainedCyp1a1expression evident in discrete populations of cells including columnar epithelia around bronchioles. Our data link diet to lung physiology and also reveal the power of bespokeCyp1a1-Flucreporters to longitudinally monitor AHR activityin vivo.