{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:51:26Z","timestamp":1791863486755,"version":"4.3.4"},"reference-count":43,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["jlr.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Lipid Research"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.jlr.2025.100840","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T15:43:48Z","timestamp":1749656628000},"page":"100840","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["An ABCB11 variant registry and novel knockin mouse model of PFIC2 based on the clinically relevant ABCB11 E297G variant"],"prefix":"10.1016","volume":"66","author":[{"given":"Eric L.","family":"Bell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-9023","authenticated-orcid":false,"given":"Jennifer K.","family":"Truong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhwa","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne","family":"Kolpak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Chunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Syverud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melida","family":"Mahinic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Durrant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Hoch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-7433","authenticated-orcid":false,"given":"Bharat","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Stoiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1493-1394","authenticated-orcid":false,"given":"John P.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert O.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair S.","family":"Garfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jlr.2025.100840_bib1","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/j.2040-4603.2013.tb00519.x","article-title":"Bile Formation and secretion","volume":"3","author":"Boyer J","year":"2013","journal-title":"Compr. Physiol."},{"key":"10.1016\/j.jlr.2025.100840_bib2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/hep.22683","article-title":"Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing","volume":"49","author":"Byrne","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100840_bib3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/3034","article-title":"A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis","volume":"20","author":"Strautnieks","year":"1998","journal-title":"Nat. Genet."},{"key":"10.1016\/j.jlr.2025.100840_bib4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jhep.2020.02.007","article-title":"Genotype correlates with the natural history of severe bile salt export pump deficiency","volume":"73","author":"van Wessel","year":"2020","journal-title":"J. Hepatol."},{"key":"10.1016\/j.jlr.2025.100840_bib5","doi-asserted-by":"crossref","first-page":"100626","DOI":"10.1016\/j.jhepr.2022.100626","article-title":"Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency","volume":"5","author":"Felzen","year":"2022","journal-title":"JHEP Rep."},{"key":"10.1016\/j.jlr.2025.100840_bib6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s10038-018-0431-1","article-title":"Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis","volume":"63","author":"Imagawa","year":"2018","journal-title":"J. Hum. Genet."},{"key":"10.1016\/j.jlr.2025.100840_bib7","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1053\/j.gastro.2008.01.038","article-title":"Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families","volume":"134","author":"Strautnieks","year":"2008","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jlr.2025.100840_bib8","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/hep.20627","article-title":"Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP\/ABCB11","volume":"41","author":"Hayashi","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100840_bib9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1186\/s13023-021-01884-4","article-title":"Epidemiology and burden of progressive familial intrahepatic cholestasis: a systematic review","volume":"16","author":"Jones-Hughes","year":"2021","journal-title":"Orphanet. J. Rare Dis."},{"key":"10.1016\/j.jlr.2025.100840_bib10","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2020.577152","article-title":"Mastermind: a comprehensive genomic association search engine for empirical evidence curation and genetic variant interpretation","volume":"11","author":"Chunn","year":"2020","journal-title":"Front. Genet."},{"key":"10.1016\/j.jlr.2025.100840_bib11","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS recommendations for the description of sequence variants: 2016 update","volume":"37","author":"den Dunnen","year":"2016","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.jlr.2025.100840_bib12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"10.1016\/j.jlr.2025.100840_bib13","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"10.1016\/j.jlr.2025.100840_bib14","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"10.1016\/j.jlr.2025.100840_bib15","doi-asserted-by":"crossref","first-page":"G58","DOI":"10.1152\/ajpgi.00367.2007","article-title":"Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells","volume":"294","author":"Kagawa","year":"2008","journal-title":"Am. J. Physiology-Gastrointestinal Liver Physiol."},{"key":"10.1016\/j.jlr.2025.100840_bib16","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/hep.21630","article-title":"4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps","volume":"45","author":"Hayashi","year":"2007","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100840_bib17","doi-asserted-by":"crossref","first-page":"C1709","DOI":"10.1152\/ajpcell.00327.2007","article-title":"Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep\/Abcb11) correlate with severity of cholestatic diseases","volume":"293","author":"Lam","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.jlr.2025.100840_bib18","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1172\/JCI0215968","article-title":"The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II","volume":"110","author":"Wang","year":"2002","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jlr.2025.100840_bib19","doi-asserted-by":"crossref","first-page":"G818","DOI":"10.1152\/ajpgi.00415.2006","article-title":"Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells","volume":"292","author":"Mochizuki","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.jlr.2025.100840_bib20","doi-asserted-by":"crossref","first-page":"24784","DOI":"10.1074\/jbc.M111.329318","article-title":"Abcb11 deficiency induces cholestasis coupled to impaired \u03b2-fatty acid oxidation in mice","volume":"287","author":"Zhang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jlr.2025.100840_bib21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"10.1016\/j.jlr.2025.100840_bib22","doi-asserted-by":"crossref","first-page":"17793","DOI":"10.1074\/jbc.M000996200","article-title":"\u03b11-Fetoprotein transcription factor is required for the expression of sterol 12\u03b1-hydroxylase, the specific enzyme for cholic acid synthesis potential role in the bile acid-mediated regulation of gene transcription","volume":"275","author":"del Castillo-Olivares","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jlr.2025.100840_bib23","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1194\/jlr.M071183","article-title":"Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans [S]","volume":"57","author":"Takahashi","year":"2016","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.jlr.2025.100840_bib24","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jhep.2015.10.024","article-title":"Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis","volume":"64","author":"Baghdasaryan","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.jlr.2025.100840_bib25","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1007\/s10354-008-0592-1","article-title":"Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases","volume":"158","author":"Trauner","year":"2008","journal-title":"Wiener Medizinische Wochenschrift"},{"key":"10.1016\/j.jlr.2025.100840_bib26","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1152\/physrev.00027.2002","article-title":"Bile salt transporters: molecular characterization, function, and regulation","volume":"83","author":"Trauner","year":"2003","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.jlr.2025.100840_bib27","article-title":"Odevixibat: a review of a bioactive compound for the treatment of pruritus approved by the FDA","volume":"15","author":"Porwal","year":"2023","journal-title":"Curr. Drug Res. Rev."},{"key":"10.1016\/j.jlr.2025.100840_bib28","article-title":"Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis","volume":"5","author":"Thompson","year":"2023","journal-title":"JHEP Rep."},{"key":"10.1016\/j.jlr.2025.100840_bib29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1053\/j.gastro.2023.03.226","article-title":"Odevixibat treatment induces biliary bile acid secretion in responsive patients with bile salt export pump deficiency","volume":"165","author":"Nomden","year":"2023","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jlr.2025.100840_bib30","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1006\/abbi.2001.2499","article-title":"Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity","volume":"393","author":"Rodr\u00edguez-Antona","year":"2001","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.jlr.2025.100840_bib31","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1053\/jhep.2002.33200","article-title":"Regulation of oxysterol 7alpha-hydroxylase (CYP7B1) in primary cultures of rat hepatocytes","volume":"35","author":"Pandak","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100840_bib32","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1194\/jlr.RA120000924","article-title":"Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition","volume":"61","author":"Kakiyama","year":"2020","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.jlr.2025.100840_bib33","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0016-5085(00)70267-8","article-title":"Regulation of sterol 12alpha-hydroxylase and cholic acid biosynthesis in the rat","volume":"118","author":"Vlahcevic","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jlr.2025.100840_bib34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1388-1981(99)00036-0","article-title":"Thyroid hormone suppresses hepatic sterol 12alpha-hydroxylase (CYP8B1) activity and messenger ribonucleic acid in rat liver: failure to define known thyroid hormone response elements in the gene","volume":"1438","author":"Andersson","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.jlr.2025.100840_bib35","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1194\/jlr.RA119000243","article-title":"A human-like bile acid pool induced by deletion of hepatic Cyp2c70 modulates effects of FXR activation in mice","volume":"61","author":"de Boer","year":"2020","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.jlr.2025.100840_bib36","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1194\/jlr.M071183","article-title":"Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans","volume":"57","author":"Takahashi","year":"2016","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.jlr.2025.100840_bib37","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.3389\/fphar.2019.01662","article-title":"CFTR modulators: the changing face of cystic fibrosis in the era of precision medicine","volume":"10","author":"Lopes-Pacheco","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jlr.2025.100840_bib38","first-page":"1489","article-title":"Severe cholestasis induced by cholic acid feeding in knockout mice of sister of P-glycoprotein","volume":"38","author":"Wang","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100840_bib39","doi-asserted-by":"crossref","first-page":"525","DOI":"10.2353\/ajpath.2007.061133","article-title":"A new xenobiotic-induced mouse model of sclerosing cholangitis and biliary fibrosis","volume":"171","author":"Fickert","year":"2007","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.jlr.2025.100840_bib40","doi-asserted-by":"crossref","first-page":"185","DOI":"10.21037\/atm.2020.01.103","article-title":"Changes in plasma bile acid profiles after partial internal biliary diversion in PFIC2 patients","volume":"8","author":"Liu","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"10.1016\/j.jlr.2025.100840_bib41","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1002\/hep.23539","article-title":"ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history","volume":"51","author":"Davit-Spraul","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.jlr.2025.100840_bib42","doi-asserted-by":"crossref","first-page":"100616","DOI":"10.1016\/j.jlr.2024.100616","article-title":"Abcb4-defect cholangitis mouse model with hydrophobic bile acid composition by in vivo liver-specific gene deletion","volume":"65","author":"Tsuruya","year":"2024","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.jlr.2025.100840_bib43","doi-asserted-by":"crossref","DOI":"10.1080\/14728214.2024.2336986","article-title":"Emerging drugs for the treatment of progressive familial intrahepatic cholestasis: a focus on phase II and III trials","author":"Hof","year":"2024","journal-title":"Expert Opin. Emerg. Drugs"}],"container-title":["Journal of Lipid Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227525001002?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022227525001002?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T15:34:24Z","timestamp":1753457664000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022227525001002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["S0022227525001002"],"URL":"https:\/\/doi.org\/10.1016\/j.jlr.2025.100840","relation":{},"ISSN":["0022-2275"],"issn-type":[{"value":"0022-2275","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"An ABCB11 variant registry and novel knockin mouse model of PFIC2 based on the clinically relevant ABCB11 E297G variant","name":"articletitle","label":"Article Title"},{"value":"Journal of Lipid Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jlr.2025.100840","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology\u00e9","name":"copyright","label":"Copyright"}],"article-number":"100840"}}