https://scholars.lib.ntu.edu.tw/handle/123456789/475136
Title: | Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump | Authors: | Wang R. HUEY-LING CHEN Liu L. Sheps J.A. Phillips M.J. Ling V. |
Issue Date: | 2009 | Journal Volume: | 50 | Journal Issue: | 3 | Start page/Pages: | 948-956 | Source: | Hepatology | Abstract: | Bile salt export pump (BSEP; ATP-binding cassette, subfamily B, member 11) mutations in humans result in progressive familial intrahepatic cholestasis type 2, a fatal liver disease with greatly reduced bile flow. However in mice, Bsep knockout leads only to mild cholestasis with substantial bile flow and up-regulated P-glycoprotein genes (multidrug resistance protein 1a [Mdr1a] and Mdr1b). To determine whether P-glycoprotein is responsible for the relatively mild phenotype observed in Bsep knockout mice, we have crossed mouse strains knocked out for Bsep and the two P-glycoprotein genes and generated a triple knockout mouse. We found that a knockout of the three genes leads to a significantly more severe phenotype with impaired bile formation, jaundice, flaccid gallbladder, and increased mortality. The triple knockout mouse is the most severe genetic model of intrahepatic cholestasis yet developed. Conclusion: P-glycoprotein functions as a critical compensatory mechanism, which reduces the severity of cholestasis in Bsep knockout mice. Copyright ? 2009 by the American Association for the Study of Liver Diseases. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-70349233968&doi=10.1002%2fhep.23089&partnerID=40&md5=86fde474cdadbf6062bd6f401c89cedc https://scholars.lib.ntu.edu.tw/handle/123456789/475136 |
ISSN: | 0270-9139 | DOI: | 10.1002/hep.23089 | SDG/Keyword: | ABC transporter; ABC transporter subfamily B member 11; glycoprotein P; multidrug resistance protein 1; multidrug resistance protein 1a; multidrug resistance protein 1b; protein bcl 2; unclassified drug; ABC transporter; Abcb11 protein, mouse; glycoprotein P; multidrug resistance protein 3; P glycoprotein 2; P-glycoprotein 2; animal experiment; animal tissue; article; bile flow; controlled study; disease severity; female; gallbladder disease; growth retardation; hepatomegaly; intrahepatic cholestasis; jaundice; knockout mouse; lymphocytic infiltration; mortality; mouse; mouse strain; nonhuman; null allele; phenotype; polymerase chain reaction; priority journal; protein function; upregulation; Western blotting; animal; bile; disease model; genetics; intrahepatic cholestasis; metabolism; mouse mutant; pathology; pathophysiology; physiology; Animals; ATP-Binding Cassette Transporters; Bile; Cholestasis, Intrahepatic; Disease Models, Animal; Mice; Mice, Knockout; P-Glycoproteins |
Appears in Collections: | 醫學教育暨生醫倫理學科所 |
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