c-fos プロトオンコゲン遺伝子におけるヌル変異のプレオトロプ的効果

R S Johnson¹, B M Spiegelman, V Papaioannou

¹Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.

Cell

|November 13, 1992

まとめ

c-fos原発がん遺伝子は,複数の組織における発達と機能に極めて重要です. ホモジゴス型変異体は重度の骨粗鬆症と発達障害を呈しますが,成人期まで生き残ることができます.

科学分野:

分子生物学は分子生物学である.
発達生物学発達生物学とは
遺伝学遺伝学とは

背景:

c-fosプロトオンコゲンは,外部刺激に対する細胞の反応において重要な役割を果たします.
c-fosの機能を理解することは,発達過程と病気を理解するために不可欠です.

研究の目的:

胚の発達と産後におけるc-fosのインビボ機能を調査する.
マウスにおけるc-fos欠乏症の現象的結果を特徴づけるために.

主な方法:

胚性幹細胞を用いた標的型c-fos変異を有するキメリックマウスの生成.
ホモジゴスC-Fos変異マウスの生殖線伝播と分析.
成長,骨格の発達,臓器機能を含むフェノタイプの特徴付け.

主要な成果:

ホモジゴスc-fos変異体は胎盤と胎児の体重が低下し,生後死亡率が高くなります.
生き残ったミュータントは,骨の骨化と歯の噴出障害によって特徴づけられる重度の骨縮症を発症します.
追加的な欠陥には,ゲメトゲネシスの遅延,リンパ性減少,および行動の変化が含まれていますが,多くは成人期まで生存します.

結論:

c-fosは,特定の組織の適切な発達と機能に不可欠であり,細胞成長には一般的に必要とされません.
オステオペトロシスやその他の発達異常は,骨格と免疫システムの発達におけるc-fosの重要な役割を強調しています.
この研究は,哺乳類の発達におけるc-fosの複雑で組織特異的な機能を強調しています.

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