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Series GSE20599 Query DataSets for GSE20599
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
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.
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.
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
Phone 713-798-6227
Organization name Baylor College of Medicine
Department Molecular and Cellular Biology
Lab SPP: Signaling Pathways Project
Street address One Baylor Plaza
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL6103 Illumina mouseRef-8 v1.1 expression beadchip
Samples (16)
GSM517333 WT.3wk.rep1
GSM517334 WT.3wk.rep2
GSM517335 FXRko.3wk.rep1
BioProject PRJNA124887

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE20599_RAW.tar 3.4 Mb (http)(custom) TAR
GSE20599_non_normalized.txt.gz 4.9 Mb (ftp)(http) TXT
Processed data included within Sample table

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