NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis.

The Journal of Experimental Medicine
Junichiro IrieWilliam M Ridgway

Abstract

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-PDC-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 9-10 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, Ab...Continue Reading

References

Mar 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S M KramsM E Gershwin
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R L CoppelM E Gershwin
Sep 1, 1987·The Journal of Clinical Investigation·R A EisenbergP L Cohen
Jan 1, 1995·Annual Review of Immunology·L S WickerL B Peterson
Apr 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D E JonesA G Diamond
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·L ChatenoudJ F Bach
Feb 1, 1993·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S TerasakiM Unoura
Dec 1, 1996·Clinical Immunology and Immunopathology·L RasoolyN R Rose
Jun 1, 1997·Research in Immunology·J F Bach, D Mathis
Aug 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S YamamotoT Abo
May 12, 2000·Immunological Reviews·M E GershwinR L Coppel
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Syuichi KoaradaWilliam M Ridgway
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patrick S C LeungM Eric Gershwin
Sep 27, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chih-Te WuJudy Van De Water
Aug 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Syuichi KoaradaWilliam M Ridgway

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Citations

Feb 26, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Shin-hyo LeeYasuhiro Kon
May 30, 2008·Clinical Reviews in Allergy & Immunology·Carlo SelmiM Eric Gershwin
Oct 27, 2010·Immunology and Cell Biology·Carlo SelmiM Eric Gershwin
Oct 12, 2007·The New England Journal of Medicine·Keith Lindor
May 22, 2009·The New England Journal of Medicine·Gideon M HirschfieldKatherine A Siminovitch
Apr 7, 2007·Current Opinion in Gastroenterology·Jacqueline G O'Leary, Daniel S Pratt
Oct 19, 2011·International Journal of Hepatology·Masashi NinomiyaTooru Shimosegawa
Jan 25, 2008·Orphanet Journal of Rare Diseases·Teru Kumagi, E Jenny Heathcote
Nov 28, 2013·Fibrogenesis & Tissue Repair·Christian LiedtkeRalf Weiskirchen
Mar 6, 2007·Immunologic Research·William M Ridgway
Jun 6, 2008·World Journal of Gastroenterology : WJG·Ana LleoM-Eric Gershwin
Jan 18, 2013·World Journal of Gastroenterology : WJG·Tian-Yan Shi, Feng-Chun Zhang
Oct 15, 2013·World Journal of Gastroenterology : WJG·Bin LiuYan Zhao
May 25, 2011·World Journal of Gastrointestinal Pathophysiology·Carlo SelmiPietro Invernizzi
May 28, 2013·International Journal of Endocrinology·Gilles WilleminKaori Minehira
Jan 26, 2013·Annual Review of Pathology·Gideon M Hirschfield, M Eric Gershwin
Nov 15, 2014·Current Pathobiology Reports·Allyson K MartínezShannon S Glaser
May 14, 2008·Cell Host & Microbe·Jochen MattnerAlbert Bendelac
Jul 25, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anna K KopecJames P Luyendyk
Jul 16, 2009·Seminars in Immunopathology·Simon HohenesterUlrich Beuers
Jun 22, 2010·Expert Opinion on Therapeutic Targets·Dipender Gill, Peng H Tan
Dec 17, 2011·Autoimmunity Reviews·Tai-Ping Lee, Bor-Luen Chiang
Aug 25, 2011·Clinics and Research in Hepatology and Gastroenterology·Axel R Concepcion, Juan F Medina
Sep 21, 2010·Gastroenterology·Gideon M HirschfieldM Eric Gershwin
Jun 29, 2010·Gastroentérologie Clinique Et Biologique·A L Mason, G Zhang
Apr 3, 2010·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Pietro InvernizziM Eric Gershwin
Oct 20, 2009·Journal of Autoimmunity·Ian R Mackay
May 27, 2008·Journal of Autoimmunity·Senga WhittinghamM Eric Gershwin
May 6, 2008·Clinics in Liver Disease·Ya-Hui ChuangM Eric Gershwin
May 6, 2008·Clinics in Liver Disease·Brian D Juran, Konstantinos N Lazaridis
May 6, 2008·Clinics in Liver Disease·Gideon M Hirschfield, E J Heathcote
Mar 14, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Ikuko HarutaKeiko Shiratori
Mar 16, 2007·Journal of Autoimmunity·Roman Rieger, M Eric Gershwin
Jul 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Patrick S C LeungUNKNOWN Acute Liver Failure Study Group
Aug 8, 2015·Journal of Autoimmunity·G J WebbG M Hirschfield
Aug 15, 2015·Cellular and Molecular Gastroenterology and Hepatology·Luca MaroniGianfranco Alpini
Oct 31, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gideon M Hirschfield, Katherine A Siminovitch
Jul 30, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Christoph P BergGerburg M Stein
Feb 3, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ana LleoM Eric Gershwin
Aug 8, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Konstantinos N LazaridisGloria M Petersen
May 9, 2008·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Teru KumagiJenny Heathcote

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Methods Mentioned

BETA
biopsy
transgenics
dissection
FACS
ELISA
irradiating
genotyping
density gradient centrifugation
electrophoresis

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