| Pancreas-specific deletion of Prox1 affects development and disrupts homeostasis of the exocrine pancreas. | |
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MedLine Citation:
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PMID: 22178591 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND & AIMS: The exocrine portion of the pancreas functions in digestion and preserves pancreatic homeostasis. Learning how this tissue forms during embryogenesis could improve our understanding of human pancreatic diseases. Expression of the homeobox gene Prox1 in the exocrine pancreas changes throughout development in mice. We investigated the role of Prox1 in development of the exocrine pancreas in mice. METHODS: Mice with pancreas-specific deletion of Prox1 (Prox1(ΔPanc)) were generated and their pancreatic tissues were analyzed using immunohistochemistry, transmission electron microscopy, histologic techniques, quantitative real-time polymerase chain reaction, immunoblotting, and morphometric analysis. RESULTS: Loss of Prox1 from the pancreas led to multiple exocrine alterations, most notably premature acinar cell differentiation, increased ductal cell proliferation, altered duct morphogenesis, and imbalanced expression of claudin proteins. Prox1(ΔPanc) mice also had some minor alterations in islet cells, but beta-cell development was not affected. The exocrine congenital defects of Prox1(ΔPanc) pancreata appeared to initiate a gradual process of deterioration that resulted in extensive loss of acinar cells, lipomatosis, and damage to ductal tissue in adult mice. CONCLUSIONS: Pancreas-specific deletion of Prox1 causes premature differentiation of acinar cells and poor elongation of epithelial branches; these defects indicate that Prox1 controls the expansion of tip progenitors in the early developing pancreas. During later stages of embryogenesis, Prox1 appears to regulate duct cell proliferation and morphogenesis. These findings identify Prox1 as an important regulator of pancreatic exocrine development. |
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Authors:
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Joby J Westmoreland; Gamze Kilic; Caroline Sartain; Sema Sirma; Jennifer Blain; Jerold Rehg; Natasha Harvey; Beatriz Sosa-Pineda |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-13 |
Journal Detail:
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Title: Gastroenterology Volume: 142 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-04-06 Completed Date: 2012-05-31 Revised Date: 2013-04-03 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 999-1009.e6 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Genetics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Aging Animals Blotting, Western Cell Differentiation Cell Proliferation Claudins / metabolism Embryonic Stem Cells / metabolism*, ultrastructure Gene Expression Regulation, Developmental Genotype Gestational Age Homeodomain Proteins / genetics Homeostasis Immunohistochemistry Islets of Langerhans / embryology, metabolism Mice Mice, Knockout Microscopy, Electron, Transmission Morphogenesis Pancreas, Exocrine / embryology, metabolism*, ultrastructure Pancreatic Ducts / embryology, metabolism Phenotype RNA, Messenger / metabolism Real-Time Polymerase Chain Reaction Tumor Suppressor Proteins / deficiency*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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5 R01DK060542/DK/NIDDK NIH HHS; R01 DK060542-08/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Claudins; 0/Homeodomain Proteins; 0/RNA, Messenger; 0/Tumor Suppressor Proteins; 0/prospero-related homeobox 1 protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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