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首页> 外文期刊>Molecular and Cellular Biology >Cited1 Is Required in Trophoblasts for Placental Development and for Embryo Growth and Survival
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Cited1 Is Required in Trophoblasts for Placental Development and for Embryo Growth and Survival

机译：滋养细胞中需要Cited1才能促进胎盘发育以及胚胎生长和存活。

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Cited1 is a transcriptional cofactor that interacts with Smad4, estrogen receptors α and β, TFAP2, and CBP/p300. It is expressed in a restricted manner in the embryo as well as in extraembryonic tissues during embryonic development. In this study we report the engineering of a loss-of-function Cited1 mutation in the mouse. Cited1 null mutants show growth restriction at 18.5 days postcoitum, and most of them die shortly after birth. Half the heterozygous females, i.e., those that carry a paternally inherited wild-type Cited1 allele, are similarly affected. Cited1 is normally expressed in trophectoderm-derived cells of the placenta; however, in these heterozygous females, Cited1 is not expressed in these cells. This occurs because Cited1 is located on the X chromosome, and thus the wild-type Cited1 allele is not expressed because the paternal X chromosome is preferentially inactivated. Loss of Cited1 resulted in abnormal placental development. In mutants, the spongiotrophoblast layer is irregular in shape and enlarged while the labyrinthine layer is reduced in size. In addition, the blood spaces within the labyrinthine layer are disrupted; the maternal sinusoids are considerably larger in mutants, leading to a reduction in the surface area available for nutrient exchange. We conclude that Cited1 is required in trophoblasts for normal placental development and subsequently for embryo viability.
机译：Cited1是与Smad4，雌激素受体α和β，TFAP2和CBP / p300相互作用的转录辅因子。它以有限的方式在胚胎以及胚胎发育过程中的胚外组织中表达。在这项研究中，我们报告了小鼠功能丧失的 Cited1 突变的工程设计。 Cited1 无效突变体在产后18.5天表现出生长受限，并且大多数在出生后不久死亡。一半杂合雌性，即那些携带父本遗传的野生型 Cited1 等位基因的雌性受到类似的影响。 Cited1 通常在胎盘的滋养外胚层细胞中表达;但是，在这些杂合子雌性中， Cited1 在这些细胞中不表达。发生这种情况的原因是 Cited1 位于X染色体上，因此未表达野生型 Cited1 等位基因，因为其父X染色体优先失活了。 Cited1 的缺失导致胎盘发育异常。在突变体中，海绵滋养层的形状不规则并扩大，而迷宫式层的尺寸减小。另外，迷宫层内的血液空间被破坏;突变体中孕妇的正弦曲线要大得多，导致可用于营养交换的表面积减少。我们得出结论，滋养细胞中的 Cited1 对于正常的胎盘发育和随后的胚胎生存力是必需的。

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