{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:42:56Z","timestamp":1791222176008,"version":"4.1.0"},"reference-count":27,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,5,15]]},"abstract":"<jats:p>Primary biliary cirrhosis (PBC) is an autoimmune disease with a strong genetic component characterized by biliary ductular inflammation with eventual liver cirrhosis. The serologic hallmark of PBC is antimitochondrial antibodies that react with the pyruvate dehydrogenase complex, targeting the inner lipoyl domain of the E2 subunit (anti\u2013PDC-E2). Herein we demonstrate that NOD.c3c4 mice congenically derived from the nonobese diabetic strain develop an autoimmune biliary disease (ABD) that models human PBC. NOD.c3c4 (at 9\u201310 wk, before significant biliary pathology) develop antibodies to PDC-E2 that are specific for the inner lipoyl domain. Affected areas of biliary epithelium are infiltrated with CD3+, CD4+, and CD8+ T cells, and treatment of NOD.c3c4 mice with monoclonal antibody to CD3 protects from ABD. Furthermore, NOD.c3c4-scid mice develop disease after adoptive transfer of splenocytes or CD4+ T cells, demonstrating a central role for T cells in pathogenesis. Histological analysis reveals destructive cholangitis, granuloma formation, and eosinophilic infiltration as seen in PBC, although, unlike PBC, the extrahepatic biliary ducts are also affected. Using a congenic mapping approach, we define the first ABD (Abd) locus, Abd1. These results identify the NOD.c3c4 mouse as the first spontaneous mouse model of PBC.<\/jats:p>","DOI":"10.1084\/jem.20051911","type":"journal-article","created":{"date-parts":[[2006,4,25]],"date-time":"2006-04-25T00:37:44Z","timestamp":1145925464000},"page":"1209-1219","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":155,"title":["NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis"],"prefix":"10.1084","volume":"203","author":[{"given":"Junichiro","family":"Irie","sequence":"first","affiliation":[{"name":"1Division of Rheumatology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehong","family":"Wu","sequence":"additional","affiliation":[{"name":"1Division of Rheumatology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda S.","family":"Wicker","sequence":"additional","affiliation":[{"name":"3Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rainbow","sequence":"additional","affiliation":[{"name":"3Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Nalesnik","sequence":"additional","affiliation":[{"name":"2Division of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Hirsch","sequence":"additional","affiliation":[{"name":"4Division of Rheumatology, Children's Hospital, Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence B.","family":"Peterson","sequence":"additional","affiliation":[{"name":"5Department of Pharmacology, Merck Research Laboratory, Rahway, NJ 07065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.C.","family":"Leung","sequence":"additional","affiliation":[{"name":"6Division of Rheumatology and Clinical Immunology, School of Medicine, University of California, Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Cheng","sequence":"additional","affiliation":[{"name":"6Division of Rheumatology and Clinical Immunology, School of Medicine, University of California, Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Mackay","sequence":"additional","affiliation":[{"name":"7Department of Biochemistry and Molecular Biology, Monash University, 3800 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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