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Experiment

Notch2 is required for proper IHBD development and morphogenesis.
Summary Data Summary
Investigator Fiorotto, Romina
Description The Notch pathway is an evolutionary conserved, intercellular signaling pathway
that plays an important role in cell fate specification and the embryonic
development of many organs, including the liver. In humans, mutations in the
Notch receptor ligand Jagged1 gene result in defective intrahepatic bile duct
(IHBD) development in Alagille syndrome. Developmental abnormalities of IHBD in
mice doubly heterozygous for Jagged1 and Notch2 mutations propose that
interactions of Jagged1 and its receptor Notch2 are crucial for normal IHBD
development. Because different cell types in the liver are involved in IHBD
development and morphogenesis, the cell-specific role of Notch signaling is not
entirely understood. We investigated the effect of combined or single targeted
disruption of Notch1 and Notch2 specifically in hepatoblasts and
hepatoblast-derived lineage cells on liver development using AlbCre transgenic
mice. Hepatocyte differentiation and homeostasis were not impaired in mice after
combined deletion of Notch1 and Notch2 (N1N2F/FAlbCre). However, we detected
irregular ductal plate structures in N1N2F/FAlbCre newborns, and further
postnatal development of IHBD was severely impaired characterized by
disorganized ductular structures accompanied by portal inflammation, portal
fibrosis, and foci of hepatocyte feathery degeneration in adulthood. Further
characterization of mutant mice with single deletion of Notch1 (N1F/FAlbCre) or
Notch2 (N2F/FAlbCre) showed that Notch2 but not Notch1 is indispensable for
normal perinatal and postnatal IHBD development. Further reduction of Notch2
gene dosage in Notch2 conditional/mutant (N2F/LacZAlbCre) animals further
enhanced IHBD abnormalities and concomitant liver pathology. Conclusion: Notch2
is required for proper IHBD development and morphogenesis. (HEPATOLOGY
2008;48:607–616.)
Status Completed
Public Release 5/11/2011
Animal Age Measured In: week(s) post-natal (w)
Flags has-data-flagSame StrainExperiment Description
Data Analysis
TypeCount
Animals37
Experimental Conditions1
Catalog Items3
Curation Info (# flags)2
Phenotype Assays3
Phenotype Measurements111
Histology Images0
Publications0
Phenotypes4


Animals
Strain NameCommon NameFemalesMalesUnknown
C57BL/6J
4
7
0
Notch2 KO
18
8
0

Animals/Strains
Experimental Factors
 Categorical Values
Name / AbbreviationDescription

Experimental Factor: Experimental Group

 Control
This animal belongs to the control group for the experiment.
 Experiment
This animal belongs to experimental group that is homozygous for gene manipulations.
Experimental Factor (Units)
Experimental Group
Experimental Factor Values


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