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| Status |
Public on Dec 10, 2010 |
| Title |
Gene expression analysis of FXR null, SHP null, and double FXR/SHP null mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Bile acid (BA) homeostasis is maintained through a feedback loop operated by the nuclear hormone receptors FXR and SHP. Here we show that contrary to the current models placing FXR upstream of SHP in a linear regulatory pathway, the phenotypic consequence of the combined loss of both receptors is much more severe than the relatively modest impact of the loss of either Fxr or Shp alone. This is highlighted by the dramatic elevation of hepatic and serum BA levels in the double knockout (DKO) mice as early as three weeks of age coupled with a commensurate increase in Cyp7A1 expression and alterations in BA homeostatic genes. In addition, we find several genes necessary for C21 steroid biosynthetic pathway as novel targets for FXR and SHP. The elevated BAs result in severe hepato-pathology but the DKO mice surprisingly do not develop complete liver failure and live for over a year. Their survival is accompanied by an adaptive proliferation of the resident liver progenitor cell population, known as oval cells. Overall, these data demonstrate that FXR and SHP function coordinately to maintain BA homeostasis, and identify DKO mice as a novel genetic model for juvenile cholestatic disorders and for oval cell activation.
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| Overall design |
Liver samples collected from FXR-/-, SHP-/-, and FXR-/-/SHP-/- animals at 3 or 5 weeks were hybridized to Illumina mouse REF-8 v1.1 arrays in duplicate.
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| Contributor(s) |
Anakk S, Moore DD |
| Citation(s) |
21123943 |
| |
| Submission date |
Mar 02, 2010 |
| Last update date |
Jun 27, 2013 |
| Contact name |
Scott Andrew Ochsner |
| E-mail(s) |
sochsner@bcm.edu
|
| Phone |
713-798-6227
|
| Organization name |
Baylor College of Medicine
|
| Department |
Molecular and Cellular Biology
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| Lab |
SPP: Signaling Pathways Project
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| Street address |
One Baylor Plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL6103 |
Illumina mouseRef-8 v1.1 expression beadchip |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA124887 |
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