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Publication : In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue.

First Author  Houten SM Year  2007
Journal  Mol Endocrinol Volume  21
Issue  6 Pages  1312-23
PubMed ID  17426284 Mgi Jnum  J:121836
Mgi Id  MGI:3712386 Doi  10.1210/me.2007-0113
Citation  Houten SM, et al. (2007) In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue. Mol Endocrinol 21(6):1312-23
abstractText  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 FXRalpha 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) FXRalpha ligands. Moreover, in vivo and in vitro analysis showed luciferase activity after GW4064 administration in the liver, kidney, and adrenal gland, indicating that FXRalpha signaling is functional in these tissues. Hepatic luciferase activity was robustly induced in cholestatic mice, showing that FXRalpha signaling pathways are activated in this disease. In conclusion, we have developed an FXR reporter mouse that is useful to monitor FXRalpha signaling in vivo in health and disease. The use of this animal could facilitate the development of new therapeutic compounds that target FXRalpha in a tissue-specific manner.
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