異常な血管新生と,タンパク質ARNTが欠けているマウスのグルコースと酸素の欠乏に対する反応

E Maltepe¹, J V Schmidt, D Baunoch

¹Department of Pathology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA.

Nature

|March 27, 1997

まとめ

アリル炭化水素受容体核転位器 (ARNT) は,低酸素とグルコースに対する反応を調節し,胚の発達に不可欠です. マウスのARNT欠乏は,発達障害と欠陥のある血管形成につながる.

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について
細胞生理学細胞生理学

背景:

ARNTは,bHLH-PASファミリーの転写因子であり,AHRとHIF-1alpha.とヘテロダイマーを形成する.
ARNT-AHRは異種生物の代謝を調節し,ARNT-HIF-1alphaは酸素欠乏反応に関与する.

研究の目的:

胚の発達と細胞反応におけるARNTの役割を調査する.
低酸素症と低血糖症のシグナル伝達経路におけるARNTの機能を明らかにする.

主な方法:

ネズミの胚性幹細胞 (ES) のアーントの位置をターゲットに破壊する.
低酸素および低血糖条件下でのArnt-/- ES細胞における遺伝子活性化の分析.
Arnt-/-胚のフェノタイプ分析.

主要な成果:

Arnt-/- ES細胞は,低酸素緊張と低血糖への反応として,遺伝子を活性化できませんでした.
Arnt-/-胚は,胚の死亡率を過去1日以上で示した 10.5.5.
欠陥の卵黄袋と枝状の血管新生,発育阻害,胚の消耗は,Arnt-/-胚で観察されました.

結論:

ARNTは胚の生存に不可欠であり,低酸素と低血糖に対する反応を調節します.
ARNTは血管新生に重要な役割を果たし,潜在的に血管内皮成長因子を通じます.
ARNTの活性化がオルガノゲネシス中の血管化を促進するモデルが提案されています.

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