ArticleHepatology (Baltimore, Md.)2018
Zebrafish abcb11b mutant reveals strategies to restore bile excretion impaired by bile salt export pump deficiency.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Liver development in Atlantic cod (Gadus morhua L.) larvae: Histomorphological analysis of biliary ABC transporters and hepatic vacuolization.Fish physiology and biochemistry · 2025Article
- Sirolimus may improve bile excretion inGenes & diseases · 2025Article
- The zebrafish in toxicology: a bibliometric analysis reveals current trends and future avenues for predictive safety assessment.Frontiers in toxicology · 2025Review
- Embryonic Amoxicillin Exposure Has Limited Impact on Liver Development but Increases Susceptibility to NAFLD in Zebrafish Larvae.International journal of molecular sciences · 2024Article
- Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib.Theranostics · 2024Article
- Autophagy modulates physiologic and adaptive response in the liver.Liver research (Beijing, China) · 2023Review
- PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish.Scientific reports · 2023Article
- Loss of Mtm1 causes cholestatic liver disease in a model of X-linked myotubular myopathy.The Journal of clinical investigation · 2023Article
- Review
- Biliary epithelial cells are facultative liver stem cells during liver regeneration in adult zebrafish.JCI insight · 2023Article
- Regenerative failure of intrahepatic biliary cells in Alagille syndrome rescued by elevated Jagged/Notch/Sox9 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Intrahepatic cholangiocyte regeneration from an Fgf-dependent extrahepatic progenitor niche in a zebrafish model of Alagille Syndrome.Hepatology (Baltimore, Md.) · 2022Article
- CRISPR-Cas9: A method for establishing rat models of drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2021Review
- Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine.Science advances · 2021Article
- Targeting the Four Pillars of Enterohepatic Bile Salt Cycling; Lessons From Genetics and Pharmacology.Hepatology (Baltimore, Md.) · 2021Review
- Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation.Stem cell reports · 2021Article
- The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.International journal of molecular sciences · 2021Review
- Expression and Function of ABC Proteins in Fish Intestine.Frontiers in physiology · 2021Review
- Molecular overview of progressive familial intrahepatic cholestasis.World journal of gastroenterology · 2020Review
- Core Hippo pathway components act as a brake on Yap and Taz in the development and maintenance of the biliary network.Development (Cambridge, England) · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
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 autophagy in both human and zebrafish hepatocytes. Treatment with rapamycin restored bile acid excretion, attenuated hepatocyte damage, and extended the life span of abcb11b mutant zebrafish, correlating with the recovery of canalicular multidrug resistance protein 1 localization.
conclusionsCollectively, these data suggest a model that rapamycin rescues BSEP-deficient phenotypes by prompting alternative transporters to excrete bile salts; multidrug resistance protein 1 is a candidate for such an alternative transporter. (Hepatology 2018;67:1531-1545).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.