Zebrafish abcb11b mutant reveals strategies to restore bile excretion impaired by bile salt export pump deficiency.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Jillian L EllisChunyue Yin

Abstract

Bile salt export pump (BSEP) adenosine triphosphate-binding cassette B11 (ABCB11) is a liver-specific ABC transporter that mediates canalicular bile salt excretion from hepatocytes. Human mutations in ABCB11 cause progressive familial intrahepatic cholestasis type 2. Although over 150 ABCB11 variants have been reported, our understanding of their biological consequences is limited by the lack of an experimental model that recapitulates the patient phenotypes. We applied CRISPR/Cas9-based genome editing technology to knock out abcb11b, the ortholog of human ABCB11, in zebrafish and found that these mutants died prematurely. Histological and ultrastructural analyses showed that abcb11b mutant zebrafish exhibited hepatocyte injury similar to that seen in patients with progressive familial intrahepatic cholestasis type 2. Hepatocytes of mutant zebrafish failed to excrete the fluorescently tagged bile acid that is a substrate of human BSEP. Multidrug resistance protein 1, which is thought to play a compensatory role in Abcb11 knockout mice, was mislocalized to the hepatocyte cytoplasm in abcb11b mutant zebrafish and in a patient lacking BSEP protein due to nonsense mutations in ABCB11. We discovered that BSEP deficiency induced auto...Continue Reading

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
May 23, 1998·The Journal of Biological Chemistry·T GerloffP J Meier
Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·F HolzingerA F Hofmann
Apr 21, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Verena KeitelRalf Kubitz
Sep 15, 2005·Biochemistry·Ping LamVictor Ling
Jul 28, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A S KniselyRichard J Thompson
Mar 26, 2008·Journal of Lipid Research·Erica J ReschlyMatthew D Krasowski
Oct 28, 2008·Current Biology : CB·Takuya F SakaguchiDidier Y R Stainier
Oct 20, 2009·European Journal of Pharmacology·V Raja Solomon, Hoyun Lee
Jan 29, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Kristin LorentMichael Pack
Mar 17, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anne Davit-SpraulEmmanuel Jacquemin
Oct 5, 2011·Developmental Biology·Juliana Debrito CartenSteven Arthur Farber
May 24, 2012·The Journal of Biological Chemistry·Yuanyuan ZhangJohn D Schuetz
Jun 22, 2012·PLoS Genetics·Marion DelousDidier Y R Stainier
Nov 13, 2012·Clinics and Research in Hepatology and Gastroenterology·Emmanuel Jacquemin
Jan 23, 2013·Gastroenterology·Shuang CuiRandolph P Matthews
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Dong FuIrwin M Arias
Nov 6, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sharon ManleyWen-Xing Ding
Nov 12, 2013·JIMD Reports·Anne Davit-SpraulEmmanuel Jacquemin
Sep 2, 2014·Developmental Biology·Danhua ZhangP Duc Si Dong
May 8, 2015·Science Translational Medicine·Kristin LorentMichael Pack
Jun 28, 2015·Journal of Hepatology·Paul Gissen, Irwin M Arias
Sep 1, 2015·Gastroenterology·Wolfram Goessling, Kirsten C Sadler
Nov 18, 2015·Expert Opinion on Therapeutic Targets·Ágnes Telbisz, László Homolya
Feb 26, 2016·Science Signaling·Pablo MardonesClaudio Hetz
Mar 10, 2017·Cellular and Molecular Gastroenterology and Hepatology·Yifeng WangTiangang Li
Mar 25, 2017·Current Topics in Developmental Biology·Shuang WangKirsten C Sadler

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Citations

Aug 22, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·M KarlgrenP Artursson
May 29, 2020·SLAS Discovery·Davide RubbiniVincenzo Di Donato
Jul 19, 2018·Frontiers in Pharmacology·Carles CornetJavier Terriente
Mar 24, 2020·The Journal of Clinical Investigation·Olivia WeeksWolfram Goessling
Jun 12, 2019·World Journal of Hepatology·Sarah Af HenkelJames E Squires
May 21, 2019·Cellular and Molecular Gastroenterology and Hepatology·Paul J WrightonWolfram Goessling
Jan 21, 2021·International Journal of Molecular Sciences·Muhammad Imran SohailPeter Chiba
Jan 2, 2021·World Journal of Gastroenterology : WJG·Sriram AmirneniRodrigo M Florentino
Nov 18, 2020·Chemical Reviews·Tim KrollLutz Schmitt
Nov 23, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Roni F KunstStan F J van de Graaf
Jul 29, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Pengcheng CaiLingfei Luo
Sep 28, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chengjian ZhaoP Duc Si Dong

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