{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T22:42:39Z","timestamp":1773960159926,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54HD090216"],"award-info":[{"award-number":["U54HD090216"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK108433; R01DK103033"],"award-info":[{"award-number":["R01DK108433; R01DK103033"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM122731; P20GM103418; P20GM103549; P30GM118247"],"award-info":[{"award-number":["P30GM122731; P20GM103418; P20GM103549; P30GM118247"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Polycystic liver disease (PLD) is characterized by the growth of numerous biliary cysts and presents in patients with autosomal dominant polycystic kidney disease (ADPKD), causing significant morbidity. Interestingly, deletion of intraflagellar transport\u2010B (IFT\u2010B) complex genes in adult mouse models of ADPKD attenuates the severity of PKD and PLD. Here we examine the role of deletion of an IFT\u2010A gene,\n                    <jats:italic>Thm1<\/jats:italic>\n                    , in PLD of juvenile and adult\n                    <jats:italic>Pkd2<\/jats:italic>\n                    conditional knockout mice. Perinatal deletion of\n                    <jats:italic>Thm1<\/jats:italic>\n                    resulted in disorganized and expanded biliary regions, biliary fibrosis, increased serum bile acids, and a shortened primary cilium on cytokeratin 19+ (CK19+) epithelial cells. In contrast, perinatal deletion of\n                    <jats:italic>Pkd2<\/jats:italic>\n                    caused PLD, with multiple CK19+ epithelial cell\u2010lined cysts, fibrosis, lengthened primary cilia, and increased Notch and ERK signaling. Perinatal deletion of\n                    <jats:italic>Thm1<\/jats:italic>\n                    in\n                    <jats:italic>Pkd2<\/jats:italic>\n                    conditional knockout mice increased hepatomegaly, liver necrosis, as well as serum bilirubin and bile acid levels, indicating enhanced liver disease severity. In contrast to effects in the developing liver, deletion of\n                    <jats:italic>Thm1<\/jats:italic>\n                    alone in adult mice did not cause a biliary phenotype. Combined deletion of\n                    <jats:italic>Pkd2<\/jats:italic>\n                    and\n                    <jats:italic>Thm1<\/jats:italic>\n                    caused variable hepatic cystogenesis at 4\u2009months of age, but differences in hepatic cystogenesis between\n                    <jats:italic>Pkd2<\/jats:italic>\n                    \u2010 and\n                    <jats:italic>Pkd2;Thm1<\/jats:italic>\n                    knockout mice were not observed by 6\u2009months of age. Similar to juvenile PLD, Notch and ERK signaling were increased in adult\n                    <jats:italic>Pkd2<\/jats:italic>\n                    conditional knockout cyst\u2010lining epithelial cells. Taken together,\n                    <jats:italic>Thm1<\/jats:italic>\n                    is required for biliary tract development, and proper biliary development restricts PLD severity. Unlike IFT\u2010B genes,\n                    <jats:italic>Thm1<\/jats:italic>\n                    does not markedly attenuate hepatic cystogenesis, suggesting differences in regulation of signaling and cystogenic processes in the liver by IFT\u2010B and \u2010A. Notably, increased Notch signaling in cyst\u2010lining epithelial cells may indicate that aberrant activation of this pathway promotes hepatic cystogenesis, presenting as a novel potential therapeutic target. \u00a9 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5685","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T10:36:20Z","timestamp":1619433380000},"page":"289-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["IFT\u2010A deficiency in juvenile mice impairs biliary development and exacerbates ADPKD liver disease"],"prefix":"10.1002","volume":"254","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-6110","authenticated-orcid":false,"given":"Tana S","family":"Pottorf","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry H","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruochen","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A","family":"Kavanaugh","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph T","family":"Cornelius","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie L","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-7164","authenticated-orcid":false,"given":"Udayan","family":"Apte","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The Liver Center, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-0685","authenticated-orcid":false,"given":"Michele T","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The Liver Center, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhulika","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-4376","authenticated-orcid":false,"given":"Pamela V","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018050493"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.07.051"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.024"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1990.01410170021003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205511"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-1056-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000477664"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-015-0327-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-015-1086-2"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0475-x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012111089"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67273"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.10.018"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02061"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.105"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30982"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00381.2017"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2715"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.05.049"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000750"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.756"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24964"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0761-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013070735"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.025791"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012821"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581818777754"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01463929"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2019.04.008"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02618288"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.04.025"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.040642"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-23-07513.1996"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.207803.112"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0156-4"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01002772"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1255354"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00064.2006"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.09.005"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23431"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.05.030"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23048"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22381"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199705)248:1<104::AID-AR12>3.0.CO;2-T"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32782-X"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2018.12.003"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.01.003"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214099"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132295"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24292"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64313"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33183"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.12.039"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150427161743"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21132-3"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.04.019"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1310842"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.46"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.3.14.2480260"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5685","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5685","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5685","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:04:41Z","timestamp":1761044681000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,21]]},"references-count":59,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/path.5685"],"URL":"https:\/\/doi.org\/10.1002\/path.5685","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.09.10.289645","asserted-by":"object"}]},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,21]]},"assertion":[{"value":"2020-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}