Document Detail


Pancreas-specific deletion of Prox1 affects development and disrupts homeostasis of the exocrine pancreas.
MedLine Citation:
PMID:  22178591     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Joby J Westmoreland; Gamze Kilic; Caroline Sartain; Sema Sirma; Jennifer Blain; Jerold Rehg; Natasha Harvey; Beatriz Sosa-Pineda
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-13
Journal Detail:
Title:  Gastroenterology     Volume:  142     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-06     Completed Date:  2012-05-31     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  999-1009.e6     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Genetics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
5 R01DK060542/DK/NIDDK NIH HHS; R01 DK060542-08/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Claudins; 0/Homeodomain Proteins; 0/RNA, Messenger; 0/Tumor Suppressor Proteins; 0/prospero-related homeobox 1 protein
Comments/Corrections

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