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.
Ishihara, Katsuhiko 1,3; Sawa, Shin-ichiro 3; Ikushima, Hideto 3; Hirota, Seiichi 4; Atsumi, Toru 2; Kamimura, Daisuke 3; Park, Sung-Joo 2; Murakami, Masaaki 3; Kitamura, Yukihiko 4; Iwakura, Yoichiro 5; Hirano, Toshio 1,2,3
[Article] International Immunology. 16(3):455-465, March 2004.

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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 MHCbright 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.

(C) Copyright Oxford University Press 2004.