| Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells. | |
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MedLine Citation:
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PMID: 19808654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1(flox/flox);VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1(flox/flox);VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1(flox/flox);VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1(flox/flox);VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine. |
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Authors:
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Chin Chen; Rixun Fang; Corrine Davis; Charalambos Maravelias; Eric Sibley |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-10-01 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 297 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-01 Completed Date: 2009-12-17 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G1126-37 Citation Subset: IM |
Affiliation:
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Stanford Univ. School of Medicine, CA 94305-5208, USA. chinchen@stanford.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Duodenum / metabolism* Enterocytes / metabolism* Enteroendocrine Cells / metabolism* Gene Expression Regulation* Goblet Cells / metabolism* Homeodomain Proteins / genetics Integrases / genetics Intestinal Mucosa / metabolism* Mice Mice, Mutant Strains Mice, Transgenic Microfilament Proteins / genetics Paneth Cells / metabolism* Promoter Regions, Genetic RNA, Messenger / metabolism Trans-Activators / deficiency*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK56339/DK/NIDDK NIH HHS; DK60715/DK/NIDDK NIH HHS; DK72416/DK/NIDDK NIH HHS; R01 DK060715-08/DK/NIDDK NIH HHS; R01 DK072416-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Homeodomain Proteins; 0/Microfilament Proteins; 0/RNA, Messenger; 0/Trans-Activators; 0/pancreatic and duodenal homeobox 1 protein; 0/villin; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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