Document Detail


Ductal malformation and pancreatitis in mice caused by conditional Jag1 deletion.
MedLine Citation:
PMID:  19208348     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Alagille syndrome is an autosomal dominant disorder caused by mutations in Notch signaling pathway genes, usually JAGGED1. Up to 40% of Alagille syndrome patients also display exocrine pancreatic insufficiency, the pathobiology of which is unknown. Additionally, no mouse model recapitulating this aspect of the disease has been reported. METHODS: We conditionally deleted both alleles of Jagged1 in the murine pancreas using Cre-loxP technology and analyzed histologic and morphologic features in postnatal and adult pancreas such as duct structure, acinar mass, and T-lymphocyte infiltration, as well as markers of pancreatic function, including fecal fat. RESULTS: Jagged1-deficient mice displayed malformed pancreatic ducts with resulting acinar cell death, fatty infiltration of the parenchyma, fibrosis, pancreatitis, and pancreatic insufficiency. CONCLUSIONS: Pancreatic ductal malformation and acinar cell loss may be responsible for pancreatic insufficiency in Jagged1-deficient mice and, by corollary, in Alagille syndrome patients.
Authors:
Maria L Golson; Kathleen M Loomes; Rebecca Oakey; Klaus H Kaestner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-01-23
Journal Detail:
Title:  Gastroenterology     Volume:  136     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1761-71.e1     Citation Subset:  AIM; IM    
Affiliation:
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / pathology
Alagille Syndrome / genetics
Animals
Calcium-Binding Proteins / genetics*,  metabolism
Gene Deletion*
Glucose / metabolism
Homeostasis
Intercellular Signaling Peptides and Proteins / genetics*,  metabolism
Membrane Proteins / genetics*,  metabolism
Mice
Mice, Knockout
Mice, Mutant Strains
Pancreas / metabolism,  pathology
Pancreatic Ducts / abnormalities*,  pathology
Pancreatitis / genetics*,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
DK055342/DK/NIDDK NIH HHS; DK071/DK/NIDDK NIH HHS; P30DK19525/DK/NIDDK NIH HHS; P30DK50306/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 134324-36-0/Serrate proteins; 50-99-7/Glucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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