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| Status |
Public on Jan 01, 2011 |
| Title |
Loss of Hepatocyte-Nuclear-Factor-1α Impacts on Adult Mouse Intestinal Epithelial Cell Growth and Cell Lineages Differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Although hepatocyte-nuclear-factor-1α (Hnf1α) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions.
Methodology/Principal Findings
An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway.
Conclusions/Significance
Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages.
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| Overall design |
HNF1alpha was knocked out. A total of 3 control and 3 mutant littermate individuals were sacrificed at 4 months of age. The jejunum was harvested and total RNA was isolated from each individual. Each RNA sample was independently used to generate probes to screen Affymetrix chips.
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| Contributor(s) |
Lussier CR, Brial F, Roy S, Langlois M, Verdu E, Rivard N, Perreault N, Boudreau F |
| Citation(s) |
20808783 |
| |
| Submission date |
Jul 20, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Francois Boudreau |
| E-mail(s) |
francois.boudreau@usherbrooke.ca
|
| 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 |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| GSM568585 |
mouse jejunum_hnf1alphacontrol_rep1 |
| GSM568586 |
mouse jejunum_hnf1alphacontrol_rep2 |
| GSM568620 |
mouse jejunum_hnf1alphacontrol_rep3 |
|
| Relations |
| BioProject |
PRJNA131179 |
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