| The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis. | |
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MedLine Citation:
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PMID: 14978019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rheumatoid arthritis (RA) is a polygenic autoimmune disease. The autoimmunity develops from synergistic actions of genetic and environmental factors. We generated a double-mutant mouse by crossing two murine models of RA, a gp130 mutant knock-in mouse (gp130F759/F759) and an HTLV-1 pX transgenic mouse (pX-Tg), in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously developed severe arthritis with a much earlier onset than the gp130F759/F759 mice and with a much higher incidence than did the pX-Tg mice. The symptoms of gp130F759/F759 mice, including lymphoadenopathy, splenomegaly, hyper-gamma-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHC(bright) CD11c+ population, were augmented in the double mutants. Marked reductions in incidence, severity and immunological abnormalities were seen in the triple mutant, IL-6-/-/gp130F759/F759/pX-Tg, indicating that the arthritis in the double mutant is IL-6 dependent. gp130F759/F759/pX-Tg is a unique mouse model for RA. |
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Authors:
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Katsuhiko Ishihara; Shin-Ichiro Sawa; Hideto Ikushima; Seiichi Hirota; Toru Atsumi; Daisuke Kamimura; Sung-Joo Park; Masaaki Murakami; Yukihiko Kitamura; Yoichiro Iwakura; Toshio Hirano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International immunology Volume: 16 ISSN: 0953-8178 ISO Abbreviation: Int. Immunol. Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-02-23 Completed Date: 2004-09-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8916182 Medline TA: Int Immunol Country: England |
Other Details:
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Languages: eng Pagination: 455-65 Citation Subset: IM |
Affiliation:
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Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Ankle Joint / pathology, radiography Antigens, CD / genetics* Arthritis, Rheumatoid / genetics*, immunology*, pathology Cytokine Receptor gp130 Disease Models, Animal Flow Cytometry Genes, pX / genetics*, immunology Human T-lymphotropic virus 1 / genetics*, immunology Interleukin-6 / immunology Lymph Nodes / cytology Membrane Glycoproteins / genetics* Mice Mice, Inbred C57BL Myeloid Cells / immunology Point Mutation* / genetics, immunology Spleen / cytology T-Lymphocyte Subsets / immunology Tyrosine / genetics |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Il6st protein, mouse; 0/Interleukin-6; 0/Membrane Glycoproteins; 133483-10-0/Cytokine Receptor gp130; 55520-40-6/Tyrosine |
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