title: Mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models.
abstract: OBJECTIVE
  A human betaretrovirus resembling the mouse mammary tumor virus (MMTV) has been characterized in primary biliary cirrhosis (PBC) and associated with aberrant pyruvate dehydrogenase complex (PDC)-E2-like expression. As MMTV is prevalent in mice as either an exogenous or endogenous infection, we tested the hypothesis that MMTV is linked with anti-mitochondrial antibody (AMA) production in models with severe immune dysfunction.
  
  
  METHODS
  Evidence for MMTV was assessed in the liver and spleen of mice by PCR and immunochemistry and PDC-E2-like protein by immunochemistry. ELISA and Western blot were used to investigate AMA and anti-MMTV antibody production.
  
  
  RESULTS
  Increased MMTV gag or env expression was detected in the livers of AMA producing mice including NOD.c3c4, CD4 directed dominant negative TGF-β receptor II and IL-2 receptor α knockout mice as well as the NOD parental strain when compared to healthy strains and biliary disease control mice. The NOD.c3c4 mice expressed MMTV surface and capsid proteins and aberrant PDC-E2-like protein in the bile ducts, whereas IL-2 receptor α knockout mice, NOD.c3c4 and the NOD mice expressed MMTV proteins and aberrant PDC-E2-like protein in the spleen. A significant correlation between anti-MMTV antibody production and AMA production was observed in the sera of NOD and NOD.c3c4 mice (p<0.0001).
  
  
  CONCLUSIONS
  The association of betaretroviral protein production and aberrant PDC-E2-like protein expression in the NOD.c3c4, NOD, and the IL-2 receptor α knockout mice is comparable to observations in patients with PBC. The correlation of AMA and anti-MMTV suggests the hypothesis that MMTV infection may trigger the production of AMA.
authors.affiliation: Department of Medicine, University of Alberta, AB, Canada.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Don
authors.initials: D
authors.lastname: Graham
authors.forename: Benchamas
authors.initials: B
authors.lastname: Subsin
authors.forename: Chelsea
authors.initials: C
authors.lastname: McDougall
authors.forename: Suzanna
authors.initials: S
authors.lastname: Gilady
authors.forename: Mark
authors.initials: M
authors.lastname: Kneteman
authors.forename: Lok
authors.initials: L
authors.lastname: Law
authors.forename: Mark
authors.initials: M
authors.lastname: Swain
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Stephen
authors.initials: S
authors.lastname: Wrzesinski
authors.forename: Richard
authors.initials: R
authors.lastname: Flavell
authors.forename: Shawn
authors.initials: S
authors.lastname: Wasilenko
authors.forename: Andrew
authors.initials: A
authors.lastname: Mason
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D051047:Dihydrolipoyllysine-Residue Acetyltransferase / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000276:immunology / Q000821:virology; D008105:Liver Cirrhosis, Biliary / Q000453:epidemiology / Q000276:immunology*; D008324:Mammary Tumor Virus, Mouse / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008928:Mitochondria / Q000276:immunology*; D024101:Mitochondrial Proteins / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D012192:Retroviridae Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D016036:Seroepidemiologic Studies; D013154:Spleen / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D001323:Autoantibodies; D024101:Mitochondrial Proteins; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; C494878:Dlat protein, mouse