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首页> 外文期刊>Molecular and Cellular Biology >Placental but Not Heart Defects Are Associated with Elevated Hypoxia-Inducible Factor α Levels in Mice Lacking Prolyl Hydroxylase Domain Protein 2
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Placental but Not Heart Defects Are Associated with Elevated Hypoxia-Inducible Factor α Levels in Mice Lacking Prolyl Hydroxylase Domain Protein 2

机译：胎盘但不是心脏缺陷与缺乏脯氨酰羟化酶域蛋白2的小鼠缺氧诱导因子α水平升高相关。

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摘要

PHD1, PHD2, and PHD3 are prolyl hydroxylase domain proteins that regulate the stability of hypoxia-inducible factor α subunits (HIF-α). To determine the roles of individual PHDs during mouse development, we disrupted all three Phd genes and found that Phd2?/? embryos died between embryonic days 12.5 and 14.5 whereas Phd1?/? or Phd3?/? mice were apparently normal. In Phd2?/? mice, severe placental and heart defects preceded embryonic death. Placental defects included significantly reduced labyrinthine branching morphogenesis, widespread penetration of the labyrinth by spongiotrophoblasts, and abnormal distribution of trophoblast giant cells. The expression of several trophoblast markers was also altered, including an increase in the spongiotrophoblast marker Mash2 and decreases in the labyrinthine markers Tfeb and Gcm1. In the heart, trabeculae were poorly developed, the myocardium was remarkably thinner, and interventricular septum was incompletely formed. Surprisingly, while there were significant global increases in HIF-α protein levels in the placenta and the embryo proper, there was no specific HIF-α increase in the heart. Taken together, these data indicate that among all three PHD proteins, PHD2 is uniquely essential during mouse embryogenesis.
机译：PHD1，PHD2和PHD3是调节低氧诱导因子α亚基（HIF-α）稳定性的 p rolyl h 羟化酶 d omain蛋白）。为了确定单个PHD在小鼠发育过程中的作用，我们破坏了所有三个 Phd 基因，发现 Phd2 ？ / ？胚胎在第12.5天和14.5天之间死亡，而 Phd1 ？/？或 Phd3 ？/ 小鼠显然是正常的。在 Phd2 ？ / ？小鼠中，严重的胎盘和心脏缺陷先于胚胎死亡。胎盘缺损包括迷宫肌分支形态的显着减少，海绵滋养层细胞对迷宫的广泛渗透以及滋养层巨细胞的异常分布。几种滋养层标志物的表达也发生了变化，包括海绵滋养层标志物 Mash2 的增加和迷宫素标志物 Tfeb 和 Gcm1 的降低。在心脏中，小梁发育不良，心肌明显变薄，室间隔未完全形成。令人惊讶的是，尽管胎盘和胚胎固有的HIF-α蛋白水平总体上显着增加，但心脏中没有特定的HIF-α升高。综上所述，这些数据表明，在所有三种PHD蛋白中，PHD2在小鼠胚胎发生过程中都是必不可少的。

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