在缺乏转录整合器p300的小鼠中,基因剂量依赖的胚胎发育和繁殖缺陷
1Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|May 20, 1998
概括
转录协激活剂p300对于小鼠发育至关重要. 它的缺失导致胚胎死亡和细胞增殖和器官形成的缺陷,突出其关键作用.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 转录辅激剂p300及其家族成员CBP调节了许多信号依赖基因表达事件.
- 基隆乙转移酶 (HAT) 活性是p300和CBP功能的一个关键特征.
研究的目的:
- 通过生成和分析缺乏功能性p300基因的小鼠来研究p300在哺乳动物发育中的重要作用.
- 确定p300缺乏对胚胎发育,细胞增殖和转录调节的影响.
主要方法:
- 用非功能性p300基因 (p300淘汰赛) 生产转基因小鼠.
- 对p300无卵性和异卵性胚胎的胚胎死亡率和发育缺陷的分析.
- 来自p300缺陷胚胎的细胞中的细胞和转录缺陷的表征.
主要成果:
- 缺乏功能性p300 (p300无菌) 的小鼠在妊娠9日至11.5天之间表现出胚胎死亡率.
- 观察到的发育缺陷包括神经发育受损,细胞增殖减少和心脏异常.
- 缺乏p300的胚胎细胞显示出特定的转录缺陷和不良的增殖.
- 令人惊的是,p300异构菌也表现出显著的胚胎致死性.
- 对p300和CBP的双重异构总是导致胚胎死亡,这表明基因对剂量敏感.
结论:
- 小鼠胚胎发育对p300和CBP的剂量非常敏感.
- 遗传证据证实,p300是一种具有基因素乙转移酶活性的联合激活剂,对于哺乳动物细胞的增殖和整体发育是不可或缺的.
- 这些发现强调了p300在基本生物过程中的关键重要性.
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