疾患モデルマウスを用いた関節リウマチの遺伝的要因の解析

• Project/Area Number: 14013012
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: 岩倉 洋一郎 東京大学, 医科学研究所, 教授 (10089120)
• Co-Investigator(Kenkyū-buntansha): 須藤 カツ子 東京大学, 医科学研究所, 助手 (50126091) ; 保田 尚孝 東京大学, 医科学研究所, 講師 (90323641)
• Project Period (FY): 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥6,600,000 (Direct Cost: ¥6,600,000); Fiscal Year 2002: ¥6,600,000 (Direct Cost: ¥6,600,000)
• Keywords: HTLV-I / IL-1Rアンタゴニスト / 関節リウマチ / IL-1 / モデルマウス / マイクロアレイ / IL-6

Research Abstract

我々はHTLV-I遺伝子を導入したTgマウス(HTLV-I-Tg)を作製し、このウイルスが関節リウマチに良く似た自己免疫性の関節炎を引き起こすことを見いだした。また、この関節炎の発症にはIL-1やIL-6な、どのサイトカインの過剰発現が重要な役割を果たしていることを示し、さらにIL-1レセプターアンタゴニスト(IL-1Ra)KOマウスも同様の自己免疫性の慢性関節炎になることを示した。本年度はこれらのモデルマウスを用いて発症関連遺伝子の網羅的探索を行った。市販の高密度オリゴアレイを利用し、両モデルマウスの関節で野生型マウスと比較して発現の変化している遺伝子を調べた結果、3倍以上の変動のある遺伝子が約1400であった。その内、発現の亢進している遺伝子が約83%、低下している遺伝子が約17%であった。また、HTLV-I-TgとIL-1RaKOでは遺伝子発現に強い相関があることが示された。バイオインフォマティクスの手法を用いてこれらの遺伝子の全長を明らかにしたところ、共通に強発現している遺伝子にはサイトカインやMMP、急性期タンパク質など炎症に関連のある遺伝子が多く含まれていたが、機能未知の遺伝子も約30見いだされた。今後はこれらの遺伝子と関節炎発症の関連を調べる予定である。

Research Products

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