サイトカイン研究のための遺伝子改変マウスライブラリーの作製

• 研究課題/領域番号: 08408037
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 実験動物学
• 研究機関: 東京大学
• 研究代表者: 岩倉 洋一郎 東京大学, 医科学研究科, 教授 (10089120)
• 研究分担者: 須藤 カツ子 東京大学, 医科学研究科, 教務職員 (50126091) ; 浅野 雅秀 東京大学, 医科学研究科, 助手 (50251450) ; 松澤 昭雄 東京大学, 医科学研究科, 教授 (50012745) ; 田川 陽一 東京大学, 医科学研究所, 教務職員 (70262079)
• 研究期間 (年度): 1996 – 1998
• 研究課題ステータス: 完了 (1998年度)
• 配分額: 20,300千円 (直接経費: 20,300千円); 1998年度: 4,700千円 (直接経費: 4,700千円); 1997年度: 5,200千円 (直接経費: 5,200千円); 1996年度: 10,400千円 (直接経費: 10,400千円)
• キーワード: トランスジェニックマウス / ノックアウトマウス / IL-1α / IL-1β / IFN-γ / IL-6 / HTLV-I / 関節リウマチ / IL-1レセプターアンタゴニスト / HTLV-L Tgマウス / HIV-Tgマウス / HTLV-I Tgマウス / IL-12 / HTLV-I-Tgマウス / HIV-I-Tgマウス

研究概要

1.炎症や免疫応答において重要な役割を果たすと考えられている、IL-1α、IL-1β、IL-1α/β、IL-1レセプターアンタゴニスト、およびIFN-γの遺伝子欠損マウスを作製することに成功した。
2.IL-1欠損マウスを用い、IL-1が末梢だけでなく中枢で発熱やグルココルチコイドの分泌制御に重要な役割を果たしていることを明らかにした。この結果は、IL-1が生体の恒常性の維持に主要な役割を果たしていることを示唆する。
3.IL-1レセプターアンタゴニスト欠損マウスは、関節リウマチによく似た自己免疫性の関節炎を発症することを明らかにした。この結果は、IL-1が免疫系の恒常性維持にも重要な役割を果たしていることを初めて示したものであり、ヒトの関節リウマチの原因の1つとして、IL-1系の異常が考えられることを示唆した。
4.関節リウマチの発症機構を、我々が独自に開発したHTLV-Iトランスジェニックマウス関節炎モデルを用いて検討し、IL-1およびIL-6が病態形成に重要な役割を果たしていることを明らかにした。この結果は、関節リウマチの治療に1つの示唆を与えるものである。
5.同じく、IFN-γ欠損マウスを用い、肝炎の発症にIFN-γが大きな役割を果たしていることを明らかにした。
6.多くの研究者との共同研究により、Mycobacteria、マウス肝炎ウイルス、Helicobacterpylori、Babesia、HSV-1、Toxoplasma、Lieshmaniaなど種々の感染症におけるIFN-γの役割を検討し、重要な役割を果たしていることを示した。また、サイトカインネットワークにおける役割を検討した。
7.IL-1についても、炎症や、HIV、マラリア、Leishmaniaなどの感染における役割を検討し、このサイトカインが病態形成に重要であることを示した。

研究成果

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