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This version published online on April 10, 2007
Molecular Endocrinology, doi:10.1210/me.2007-0113
A more recent version of this article appeared on June 1, 2007
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Submitted on February 28, 2007
Accepted on April 4, 2007

In vivo imaging of FXR activity reveals the ileum as the primary bile acid signaling tissue

Sander M. Houten, David H. Volle, Carolyn L. Cummins, David J. Mangelsdorf, and Johan Auwerx*

Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), CNRS / INSERM / ULP; Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Rd., Dallas, TX 75390, USA; Institut Clinique de la Souris, 1 Rue Laurent Fries, 67404 Illkirch, France; Hôpitaux Universitaires de Strasbourg, Laboratoire de Biochimie Générale et Spécialisée, Strasbourg, France

* To whom correspondence should be addressed. E-mail: auwerx{at}igbmc.u-strasbg.fr.

We generated and characterized a firefly luciferase reporter mouse for the nuclear receptor farnesoid X receptor (FXR). This FXR reporter mouse has basal luciferase expression in the terminal ileum, an organ with well-characterized FXR{alpha} signaling. In vivo luciferase activity reflected the diurnal activity pattern of the mouse, and is regulated by both natural (bile acids; chenodeoxycholic acid) and synthetic (GW4064) FXR{alpha} ligands. Moreover, in vivo and in vitro analysis showed luciferase activity following GW4064 administration in the liver, kidney and adrenal gland, indicating that FXR{alpha} signaling is functional in these tissues. Hepatic luciferase activity was robustly induced in cholestatic mice, showing that FXR{alpha} signaling pathways are activated in this disease. In conclusion, we have developed an FXR reporter mouse that is useful to monitor FXR{alpha} signaling in vivo in health and disease. The use of this animal could facilitate the development of new therapeutic compounds that target FXR{alpha} in a tissue-specific manner.
Key words: In vivo imaging • luciferase • gene expression • FXR • nuclear receptor

NURSA Molecule Pages Link:

Nuclear Receptors:   FXRα
Ligands:   GW4064



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