{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:20:57Z","timestamp":1789230057414,"version":"build-2803163510"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>A recent multicenter genetic exploration of the biliary atresia splenic malformation syndrome identified mutations in the ciliary gene <jats:italic toggle=\"yes\">PKD1L1<\/jats:italic> as candidate etiologic contributors. We hypothesized that deletion of <jats:italic toggle=\"yes\">Pkd1l1<\/jats:italic> in developing hepatoblasts would lead to cholangiopathy in mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>CRISPR-based genome editing inserted <jats:italic toggle=\"yes\">loxP<\/jats:italic> sites flanking exon 8 of the murine <jats:italic toggle=\"yes\">Pkd1l1<\/jats:italic> gene. <jats:italic toggle=\"yes\">Pkd1l1<\/jats:italic>\n                                 <jats:sup>\n                                    Fl\/Fl\n                                 <\/jats:sup> cross-bred with alpha-fetoprotein-Cre expressing mice to generate a liver-specific intrahepatic <jats:italic toggle=\"yes\">Pkd1l1<\/jats:italic>-deficient model (LKO). From embryonic day 18 through week 30, control (<jats:italic toggle=\"yes\">Fl\/Fl<\/jats:italic>) and LKO mice were evaluated with standard serum chemistries and liver histology. At select ages, tissues were analyzed using RNA sequencing, immunofluorescence, and electron microscopy with a focus on biliary structures, peribiliary inflammation, and fibrosis. Bile duct ligation for 5 days of <jats:italic toggle=\"yes\">Fl\/Fl<\/jats:italic> and LKO mice was followed by standard serum and liver analytics. Histological analyses from perinatal ages revealed delayed biliary maturation and reduced primary cilia, with progressive cholangiocyte proliferation, peribiliary fibroinflammation, and arterial hypertrophy evident in 7- to 16-week-old LKO versus <jats:italic toggle=\"yes\">Fl\/Fl<\/jats:italic> livers. Following bile duct ligation, cholangiocyte proliferation, peribiliary fibroinflammation, and necrosis were increased in LKO compared with <jats:italic toggle=\"yes\">Fl\/Fl<\/jats:italic> livers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Bile duct ligation of the <jats:italic toggle=\"yes\">Pkd1l1<\/jats:italic>-deficient mouse model mirrors several aspects of the intrahepatic pathophysiology of biliary atresia in humans including bile duct dysmorphogenesis, peribiliary fibroinflammation, hepatic arteriopathy, and ciliopathy. This first genetically linked model of biliary atresia, the <jats:italic toggle=\"yes\">Pkd1l1<\/jats:italic> LKO mouse, may allow researchers a means to develop a deeper understanding of the pathophysiology of this serious and perplexing disorder, including the opportunity to identify rational therapeutic targets.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/hep.0000000000000029","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T09:00:34Z","timestamp":1673859634000},"page":"1274-1286","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":24,"title":["Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy"],"prefix":"10.1097","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2793-399X","authenticated-orcid":false,"given":"Dominick 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