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Experiment

Cobas Order # 2432
Summary Data Summary
Investigator CAI, SHI-YING
Description Deficiency of ABCB4 is associated with several forms of cholestasis in humans.
Abcb4-/- mice also develop cholestasis, but it remains uncertain what role other
canalicular transporters play in the development of this disease. We examined
the expression of these transporters in Abcb4-/- mice compared with their
wild-type littermate controls at ages of 10 days and 3, 6, and 12 wk. Elevated
plasma bile acid levels were already detected at 10 days and at all ages
thereafter in Abcb4-/- mice. The expression of Bsep, Mrp2, Atp8b1, Abcg5, and
Abcg8 liver proteins did not change at 10 days, but Bsep, Mrp2, and Atp8b1 were
reduced, whereas Abcg5 and Abcg8 expression were increased in Abcb4-/- mice at
all later ages. Lower bile acid concentrations were also detected in the bile of
6-wk-old Abcb4-/- mice. Immunofluorescence labeling revealed distorted
canalicular architecture in the liver tissue by 12 wk in Abcb4-/- mice. Whereas
Bsep and Mrp2 remained associated with the apical membrane, Atp8b1 was now
localized in discrete punctuate structures adjacent to the canalicular membrane
in these mice. Expression of Bsep mRNA was increased in the livers of 10-day-old
Abcb4-/- mice, whereas Ost-a was decreased. By 12 wk, Bsep, Mrp2, and Abcg5 mRNA
were all increased, whereas Ost-a and Ntcp were reduced. These findings indicate
that canalicular transporters that determine the formation of bile are altered
early in the development of cholestasis in Abcb4-/- mice and may contribute to
the pathogenesis of cholestasis in this disorder.

Applicable research area(s): Digestive
Status Completed
Public Release 2/3/2014
Animal Age Measured In: month(s) post-natal (m)
Flags has-data-flagSame StrainExperiment Description
Data Analysis
TypeCount
Animals44
Experimental Conditions1
Catalog Items2
Curation Info (# flags)2
Phenotype Assays2
Phenotype Measurements88
Histology Images0
Publications0
Phenotypes1


Animals
Strain NameCommon NameFemalesMalesUnknown
FVB/NJ
0
12
0
FVB.129P2-Abcb4tm1Bor/J
0
32
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


Phenotype Assays Add / Edit


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