{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:27:04Z","timestamp":1791624424392,"version":"4.3.4"},"reference-count":40,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000264","name":"Canadian Liver Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000264","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006458","name":"Children's Hospital of Philadelphia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012280","name":"Rare Disease Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012280","id-type":"DOI","asserted-by":"crossref"}]},{"name":"BC Children's Hospital Foundation"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["FDN-167285"],"award-info":[{"award-number":["FDN-167285"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006126","name":"The Hospital for Sick Children","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006126","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Biliary atresia is a fibroinflammatory neonatal disease with no effective therapies. A subset of cases (10-20%) is associated with laterality defects \u2013 labeled biliary atresia splenic malformation (BASM) syndrome. Recently, whole-exome sequencing of patients with BASM identified deleterious variants in PKD1L1. PKD1L1 is involved in left-right axis determination; however, its role in cholangiocytes is unknown. We generated the pkd1l1hsc117 allele using CRISPR\/Cas9 mutagenesis in zebrafish to determine the role of Pkd1l1 in biliary development and function. Wild-type and mutant larvae were assessed for laterality defects, biliary function and biliary tree architecture at 5\u2005days post fertilization. pkd1l1hsc117 mutant larvae exhibited early left-right patterning defects. The gallbladder was positioned on the left in 47% of mutants compared to 4% of wild-type larvae. Accumulation of PED6 in the gallbladder, an indicator of hepatobiliary function, was significantly reduced in pkd1l1hsc117 mutants (46%) compared to wild-type larvae (4%). pkd1l1hsc117 larvae exhibited fewer biliary epithelial cells and reduced density of the intrahepatic biliary network compared to those in wild-type larvae. These data highlight the essential role of pkd1l1 in normal development and function of the zebrafish biliary system, supporting a role for this gene as a cause of BASM.<\/jats:p>","DOI":"10.1242\/dmm.049326","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T07:49:01Z","timestamp":1694072941000},"source":"Crossref","is-referenced-by-count":7,"title":["Loss of zebrafish <i>pkd1l1<\/i> causes biliary defects that have implications for biliary atresia splenic malformation"],"prefix":"10.1242","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-3268","authenticated-orcid":false,"given":"Rouknuddin Q.","family":"Ali","sequence":"first","affiliation":[{"name":"The Hospital for Sick Children 1 Program in Developmental & Stem Cell Biology , , Toronto, ON M5G 0A4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Meyer-Miner","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children 1 Program in Developmental & Stem Cell Biology , , Toronto, ON M5G 0A4 , Canada"},{"name":"The University of Toronto 2 Department of Molecular Genetics , , Toronto, ON M5S 1A8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"David-Rachel","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children 1 Program in Developmental & Stem Cell Biology , , Toronto, ON M5G 0A4 , Canada"},{"name":"The University of Toronto 2 Department of Molecular Genetics , , Toronto, ON M5S 1A8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona J. H.","family":"Lee","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children 1 Program in Developmental & Stem Cell Biology , , Toronto, ON M5G 0A4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Philadelphia 3 Department of Pathology and Laboratory Medicine , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul J.","family":"Karpen","sequence":"additional","affiliation":[{"name":"University School of Medicine and Children's Healthcare of Atlanta 4 Department of Pediatrics Emory , , Atlanta, GA 30322 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Ciruna","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children 1 Program in Developmental & Stem Cell Biology , , Toronto, ON M5G 0A4 , Canada"},{"name":"The University of Toronto 2 Department of Molecular Genetics , , Toronto, ON M5S 1A8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Ghanekar","sequence":"additional","affiliation":[{"name":"University Health Network, Toronto, ON M5C 2C4 5 Division of General Surgery , , Canada"},{"name":"6 Department of Surgery, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"University of Toronto 7 Department of Surgery , , Toronto, ON M5T 1P5 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-5023","authenticated-orcid":false,"given":"Binita M.","family":"Kamath","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children 1 Program in Developmental & Stem Cell Biology , , Toronto, ON M5G 0A4 , Canada"},{"name":"Hepatology and Nutrition, The Hospital for Sick Children 8 Division of Gastroenterology , , Toronto, ON M5G 1X8 , Canada"},{"name":"University of Toronto 9 Department of Pediatrics , , Toronto, ON M5G 1X8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"2023101107541006500_DMM049326C1","doi-asserted-by":"publisher","first-page":"e0150188","DOI":"10.1371\/journal.pone.0150188","article-title":"Homology directed knockin of point mutations in the zebrafish tardbp and fus genes in ALS using the CRISPR\/Cas9 system","volume":"11","author":"Armstrong","year":"2016","journal-title":"PLoS One"},{"key":"2023101107541006500_DMM049326C2","doi-asserted-by":"publisher","first-page":"140081","DOI":"10.1016\/j.scitotenv.2020.140081","article-title":"Sub-chronic carbendazim exposure induces hepatic glycolipid metabolism disorder accompanied by gut microbiota dysbiosis in adult zebrafish (Daino rerio)","volume":"739","author":"Bao","year":"2020","journal-title":"Sci. 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