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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Zhang, G; Chen, M; Graham, D; Subsin, B; McDougall, C; Gilady, S; Kneteman, M; Law, L; Swain, M; Trauner, M; Wrzesinski, S; Flavell, R; Wasilenko, S; Mason, A.
Mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models.
J Hepatol. 2011; 55(4):876-884 Doi: 10.1016/j.jhep.2011.01.037
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Co-Autor*innen der Med Uni Graz
Trauner Michael
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Abstract:
Background & Aims: 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-beta receptor II and IL-2 receptor alpha 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 alpha 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 alpha 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. Crown copyright (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Autoantibodies - blood Autoantibodies - immunology
Dihydrolipoyllysine-Residue Acetyltransferase - genetics
Disease Models, Animal -
Female -
Liver - immunology Liver - virology
Liver Cirrhosis, Biliary - epidemiology Liver Cirrhosis, Biliary - immunology
Mammary Tumor Virus, Mouse - growth and development Mammary Tumor Virus, Mouse - immunology
Mice -
Mice, Inbred BALB C -
Mice, Inbred C3H -
Mice, Inbred C57BL -
Mice, Inbred NOD -
Mice, Knockout -
Mitochondria - immunology
Mitochondrial Proteins - genetics
Receptors, Interleukin - genetics
Retroviridae Infections - diagnosis Retroviridae Infections - epidemiology Retroviridae Infections - immunology
Seroepidemiologic Studies -
Spleen - immunology Spleen - virology
Tumor Virus Infections - diagnosis Tumor Virus Infections - epidemiology Tumor Virus Infections - immunology
Virus Replication - physiology

Find related publications in this database (Keywords)
Primary biliary cirrhosis
NOD.c3c4
PBC mouse model
Mouse mammary tumor virus
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