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Series GSE11759 Query DataSets for GSE11759
Status Public on Dec 01, 2008
Title Role of HNF4alpha in the adult colon
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background & Aims: HNF4α is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4α deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4α. Methods: A conditional intestinal epithelial Hnf4α knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4α intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4α null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4α colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4α mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4α in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation.
Overall design HNF4alpha was conditionally knockout in the mouse epithelial colon with the villin CRE. A total of 3 control and 3 mutant littermates individuals were sacrificed at 1 year of age. The colon was harvested and Total RNA was isolated from each individuals. Each RNA sample was independently used to generate probes to screen affymetrix chips.
Contributor(s) Darsigny M, Babeu J, Dupuis A, Furth EE, Seidman EG, Levy E, Gendron F, Boudreau F
Citation(s) 19898610
Submission date Jun 11, 2008
Last update date Feb 11, 2019
Contact name Francois Boudreau
Phone 819-820-6876
Fax 819-564-5320
Organization name University of Sherbrooke
Department Anatomy and Cell Biology
Lab Boudreau
Street address 3001 12e ave Nord
City Sherbrooke
State/province Quebec
ZIP/Postal code J1H 5N4
Country Canada
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM297808 mouse colon_hnf4mutant_rep1
GSM297817 mouse colon_hnf4control_rep1
GSM297818 mouse colon_hnf4control_rep2
BioProject PRJNA106055

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE11759_RAW.tar 35.8 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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