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

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

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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 FXRα 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) FXRα ligands. Moreover, in vivo and in vitro analysis showed luciferase activity after GW4064 administration in the liver, kidney, and adrenal gland, indicating that FXRα signaling is functional in these tissues. Hepatic luciferase activity was robustly induced in cholestatic mice, showing that FXRα signaling pathways are activated in this disease. In conclusion, we have developed an FXR reporter mouse that is useful to monitor FXRα signaling in vivo in health and disease. The use of this animal could facilitate the development of new therapeutic compounds that target FXRα in a tissue-specific manner.

Original languageEnglish (US)
Pages (from-to)1312-1323
Number of pages12
JournalMolecular Endocrinology
Volume21
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Bile Acids and Salts
Ileum
Luciferases
Firefly Luciferases
Chenodeoxycholic Acid
Liver
Cytoplasmic and Nuclear Receptors
Adrenal Glands
Ligands
Kidney
Health
GW 4064
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue. / Houten, Sander M.; Volle, David H.; Cummins, Carolyn L.; Mangelsdorf, David J.; Auwerx, Johan.

In: Molecular Endocrinology, Vol. 21, No. 6, 06.2007, p. 1312-1323.

Research output: Contribution to journalArticle

Houten, Sander M. ; Volle, David H. ; Cummins, Carolyn L. ; Mangelsdorf, David J. ; Auwerx, Johan. / In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue. In: Molecular Endocrinology. 2007 ; Vol. 21, No. 6. pp. 1312-1323.
@article{8ae882dd69b64b4ba18de4d0960cba74,
title = "In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue",
abstract = "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 FXRα 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) FXRα ligands. Moreover, in vivo and in vitro analysis showed luciferase activity after GW4064 administration in the liver, kidney, and adrenal gland, indicating that FXRα signaling is functional in these tissues. Hepatic luciferase activity was robustly induced in cholestatic mice, showing that FXRα signaling pathways are activated in this disease. In conclusion, we have developed an FXR reporter mouse that is useful to monitor FXRα signaling in vivo in health and disease. The use of this animal could facilitate the development of new therapeutic compounds that target FXRα in a tissue-specific manner.",
author = "Houten, {Sander M.} and Volle, {David H.} and Cummins, {Carolyn L.} and Mangelsdorf, {David J.} and Johan Auwerx",
year = "2007",
month = "6",
doi = "10.1210/me.2007-0113",
language = "English (US)",
volume = "21",
pages = "1312--1323",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue

AU - Houten, Sander M.

AU - Volle, David H.

AU - Cummins, Carolyn L.

AU - Mangelsdorf, David J.

AU - Auwerx, Johan

PY - 2007/6

Y1 - 2007/6

N2 - 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 FXRα 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) FXRα ligands. Moreover, in vivo and in vitro analysis showed luciferase activity after GW4064 administration in the liver, kidney, and adrenal gland, indicating that FXRα signaling is functional in these tissues. Hepatic luciferase activity was robustly induced in cholestatic mice, showing that FXRα signaling pathways are activated in this disease. In conclusion, we have developed an FXR reporter mouse that is useful to monitor FXRα signaling in vivo in health and disease. The use of this animal could facilitate the development of new therapeutic compounds that target FXRα in a tissue-specific manner.

AB - 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 FXRα 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) FXRα ligands. Moreover, in vivo and in vitro analysis showed luciferase activity after GW4064 administration in the liver, kidney, and adrenal gland, indicating that FXRα signaling is functional in these tissues. Hepatic luciferase activity was robustly induced in cholestatic mice, showing that FXRα signaling pathways are activated in this disease. In conclusion, we have developed an FXR reporter mouse that is useful to monitor FXRα signaling in vivo in health and disease. The use of this animal could facilitate the development of new therapeutic compounds that target FXRα in a tissue-specific manner.

UR - http://www.scopus.com/inward/record.url?scp=34250894871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250894871&partnerID=8YFLogxK

U2 - 10.1210/me.2007-0113

DO - 10.1210/me.2007-0113

M3 - Article

C2 - 17426284

AN - SCOPUS:34250894871

VL - 21

SP - 1312

EP - 1323

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 6

ER -