Apaf1 (CED-4同型) は,哺乳類の発達におけるプログラム細胞死を調節する
F Cecconi1, G Alvarez-Bolado, B I Meyer
1Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany.
Cell
|September 30, 1998
まとめ
アポプトティックプロテアゼ活性化因子1 (Apaf1) は,哺乳類の発達に極めて重要です. 欠乏すると,胚の致死性や,プログラム細胞死障害による重度の発達障害が生じます.
科学分野:
- 発達生物学 発達生物学について
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- アポプトシスプロテアゼ活性化因子1 (Apaf1) は,本来のアポプトシス経路の重要な構成要素です.
- カスパース9 (CASP9) の活性化を媒介し,その後,カスパース3 (CASP3) の活性化を媒介する.
- 哺乳類の胚発育とプログラム細胞死におけるApaf1の役割は完全に理解されていません.
研究 の 目的:
- 哺乳類の胚発達におけるApaf1の機能を調査する.
- 胚形成中のプログラム細胞死におけるApaf1の役割を決定する.
主な方法:
- ネズミのApaf1.1.の遺伝子トラップヌルアルレルの生成
- ホモサイゴスなApaf1変異体胚のフェノタイプ分析.
- カスパース3活性化のインサイト免疫検知.
主要な成果:
- ホモジゴスなApaf1変異体は16.5.日に胚の致死性を示す.
- ミュータントは,重度の頭蓋骨・顔の異常,脳の過剰成長,持続的な指間網,および眼の異常を呈する.
- Apaf1欠乏は,線維芽細胞のアポプトシス反応を低下させ,生体内でカスパース3の活性化を阻害する.
結論:
- Apaf1は,胚の脳におけるカスパース3の活性化に不可欠である.
- Apaf1は,哺乳類の発達プログラム細胞死を調節する上で重要な役割を果たしています.
- Apaf1の欠如は,重度の発達障害と胚の致死につながる.
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