Cited1 is required in trophoblasts for placental development and for embryo growth and survival
Cited1 is required in trophoblasts for placental development and for embryo growth and survival
复制标题
DOI：
10.1128/mcb.24.1.228-244.2004
复制
发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Dunwoodie, SL
中科院分区：
文献类型：
--
作者：
Rodriguez, TA;Sparrow, DB;Dunwoodie, SL
Cited 1是一种转录辅因子，与Smad 4、雌激素受体α和β、TFAP 2和CBP/p300相互作用。在胚胎发育过程中，它在胚胎和胚外组织中以有限的方式表达。在这项研究中，我们报告了在小鼠中的功能丧失的Cited 1突变的工程。Cited 1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。一半的杂合子女性，即，那些携带父系遗传的野生型Cited 1等位基因的人也受到类似的影响。Cited 1通常在胎盘的滋养外胚层来源的细胞中表达;然而，在这些杂合女性中，Cited 1在这些细胞中不表达。这是因为Cited 1位于X染色体上，因此野生型Cited 1等位基因不表达，因为父本X染色体优先失活。Cited 1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增大，而胎盘层的大小减小。此外，谷胱甘肽层内的血液空间被破坏;突变体中的母体血窦相当大，导致可用于营养交换的表面积减少。我们的结论是，Cited 1所需的滋养层正常胎盘发育和随后的胚胎活力。
Cited1 is a transcriptional cofactor that interacts with Smad4, estrogen receptors alpha and beta, 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.