ミエリンベースのタンパク質に特異的なT細胞受容体を発現するトランス遺伝子マウスは,自発的な自己免疫を発達させる
J Goverman1, A Woods, L Larson
1Division of Biology, California Institute of Technology, Pasadena 91125.
Cell
|February 26, 1993
まとめ
研究者は,多発性硬化症 (MS) の新しいマウスモデルを作成し,自発的に病気を発症します. このモデルは,MSのような自己免疫疾患に寄与する遺伝的および環境的要因を研究するのに役立ちます.
科学分野:
- 免疫学 免疫学とは
- 神経科学は神経科学である.
- 遺伝学 遺伝学とは
背景:
- 多発性硬化症 (MS) は,中枢神経系に影響を与える複雑な自己免疫疾患です.
- 現在の動物モデルでは,しばしば特定の誘導方法が必要であり,自発的な疾患の研究を制限しています.
- 遺伝的および環境的トリガーの理解は,新しいMS治療法の開発に不可欠です.
研究 の 目的:
- ヒトの多発性硬化症を模倣した自己免疫疾患を自発的に発症させる新しいトランスジェニックマウスモデルを開発する.
- 疾患発現におけるミエリン塩基タンパク質 (MBP) に特異的な自己反応性T細胞の役割を調査する.
- 自発的自己免疫病原性における遺伝的傾向と環境要因の相互作用を探求する.
主な方法:
- ミエリンベースのタンパク質 (MBP) に特異的な再編成されたT細胞受容体を発現するトランスジェニックマウスの構築.
- リンパ性臓器におけるT細胞耐性誘導と自己反応性T細胞の存在の評価.
- 実験的なアレルギー性脳髄炎 (EAE) の誘導には,MBP,補助剤, pertussis toxin を使用する.
- 特定の病原体フリー (SPF) 環境と従来の環境で飼育されたマウスにおける自発的なEAE発達の比較.
主要な成果:
- トランスジェニックマウスは,周辺T細胞の耐性がないことを示し,機能的,自己反応性T細胞を持っていた.
- マウスは,MBPと補助性/百日咳毒素,または百日咳毒素単独で免疫されたときにEAEを発症した.
- 自発的なEAEは,非不妊状態のマウスで発生したが,不妊でSPF環境では予防された.
- これは,このモデルにおける自己免疫疾患の自発的な発症に環境要因が重要なことを示しています.
結論:
- 開発されたトランスジェニックマウスモデルは,ヒトの多発性硬化症に似た自発的な自己免疫疾患を効果的に再現しています.
- 微生物への曝露などの環境要因は,遺伝的に感受性の高い個体で自己免疫疾患を誘発するのに重要な役割を果たします.
- このモデルは,自発的な自己免疫疾患の根底にある複雑な遺伝子と環境の相互作用を解剖するための貴重なプラットフォームを提供します.
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