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Publication
Altered expression and function of canalicular transporters during early
development of cholestatic liver injury in Abcb4-deficient mice.
Authors Cai SY, Mennone A, Soroka CJ, Boyer JL
Submitted By Submitted Externally on 8/9/2017
Status Published
Journal American journal of physiology. Gastrointestinal and liver physiology
Year 2014
Date Published 4/15/2014
Volume : Pages 306 : G670 - 6
PubMed Reference 24481602
Abstract 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.




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