| Project/Area Number |
10558120
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory animal science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IWAKURA Yoichiro Institute of Medical Science, Center for Experimental Medicine, The University of Tokyo Professor, 医科学研究所, 教授 (10089120)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Susumu Nipponn Institute for Biological Science, Director, (Scientist), 所長(研究職)
SUDO Katsuko Institute of Medical Science, Center for Experimental Medicine, The University of Tokyo Research associate, 医科学研究所, 教務職員 (50126091)
安田 二郎 (安田 二朗) 東京大学, 医科学研究所, 助手 (10282518)
浅野 雅秀 金沢大学, 医学部, 教授 (50251450)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Rheumatoid arthritis / transgenic mice / knockout mice / HTLV-I / IL-1 / IL-6 / antoimmune disease / model mice / 疾患モデル / サイトカイン / HTLV-I-Tgマウス / コンジェニック / IL-1レセプターアンタゴニスト |
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| Research Abstract |
Disease models are important to analyze pathogenesis of the disease and to develop effective medication. It is important for the disease models to represent faithfully the symptoms of the disease. Thus, to develop disease model, it is important to characterize the pathogenesity of the disease in order to show similarity to human cases. Previously, we reported that HTLV-I-Tg mice developed rheumatoid-like inflammatory arthropathy, and suggested involvement of autoimmunity in the pathogenesity. In this report, to elucidate pathogenesis of arthritis, we produced Tg mice that expressed tax gene in T cell or macrophage by constructing DNAs that express the tax gene alone under the control of either CD4 enhancer/promoter or c-fms promoter. The tax gene was expressed in T cells and in macrophages in CD4-tax-Tg mice, and these mice developed not only arthritis, but also autoimmunity. On the other hand, the transgene was determined in macrophages in fms-tax mice, and 100% of the mice developed arthritis at the age of 2 months. Transplantation of bone marrow cells from these mice could induce arthritis in wild type mice suggesting that the synovial cells that originated from bone marrow cells are abnormal in these Tg mice. Thus, it is shown that not only LTR-pX mice, but also fms-tax mice are both valuable models for human rheumatoid arthritis.
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