Document Detail


Notch signaling regulates bile duct morphogenesis in mice.
MedLine Citation:
PMID:  18365007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heterozygous for Jag1 and Notch2 mutations are an excellent model for Alagille syndrome. However, our previous study did not establish whether bile duct paucity in Jag1/Notch2 double heterozygous mice resulted from impaired differentiation of bile duct precursor cells, or from defects in bile duct morphogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterize embryonic biliary tract formation in our previously described Jag1/Notch2 double heterozygous Alagille syndrome model, and describe another mouse model of bile duct paucity resulting from liver-specific deletion of the Notch2 gene. CONCLUSIONS/SIGNIFICANCE: Our data support a model in which bile duct paucity in Notch pathway loss of function mutant mice results from defects in bile duct morphogenesis rather than cell fate specification.
Authors:
Julie Lozier; Brent McCright; Thomas Gridley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-03-26
Journal Detail:
Title:  PloS one     Volume:  3     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2008  
Date Detail:
Created Date:  2008-03-26     Completed Date:  2008-08-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1851     Citation Subset:  IM    
Affiliation:
The Jackson Laboratory, Bar Harbor, Maine, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile Ducts / growth & development*
Heterozygote
Immunohistochemistry
Mice
Morphogenesis*
Receptors, Notch / genetics,  metabolism*
Signal Transduction*
Grant Support
ID/Acronym/Agency:
DK066387/DK/NIDDK NIH HHS; NS036437/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Notch
Comments/Corrections

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