Plac1 (placenta-specific 1) is essential for normal placental and embryonic development.
Plac1 (placenta-specific 1) is essential for normal placental and embryonic development.
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DOI：
10.1002/mrd.22062
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发表时间：
2012-08
影响因子：
2.5
通讯作者：
Fant ME
中科院分区：
文献类型：
--
作者：
Jackman SM;Kong X;Fant ME
Plac 1是最近发现的X连锁基因，其表达主要限于滋养层细胞谱系。它定位于先前与胎盘生长有关的染色体位点。因此，我们试图通过检查突变小鼠模型来确定Plac 1是否是胎盘和胚胎发育所必需的。Plac 1消融导致胎盘肥大和轻度宫内生长迟缓（IUGR）。在E16.5时，从母体遗传的Plac 1-null等位基因（Xm-X）的敲除（KO）和杂合（Het）胎盘比野生型（WT）胎盘重约100%，而相应的胚胎重量轻7-12%。相比之下，从父亲（XXp-）继承无效等位基因的Het胎盘表现出正常生长，并且在组织学上与WT胎盘无法区分，这与Plac 1的父系印记一致。在整个妊娠期间检查时，WT和Xm-X胎盘重量在E16.5达到峰值，此后略有下降。然而，KO胎盘（Xm-Xp-和Xm-Y）在E16.5后重量继续增加，这与父本Plac 1等位基因的功能作用一致。随后的分析证实，父亲的等位基因部分逃脱完全的X-失活，从而有助于胎盘生长调节。此外，尽管雄性Plac 1 KO小鼠可以存活，但由于妊娠后期或出生后不久发生的事件，它们表现出活力下降。因此，Plac 1是一个父方印记的X连锁基因，对正常胎盘和胚胎发育至关重要。
Plac1 is a recently identified, X-linked gene whose expression is restricted primarily to cells of trophoblast lineage. It localizes to a chromosomal locus previously implicated in placental growth. We therefore sought to determine if Plac1 is necessary for placental and embryonic development by examining a mutant mouse model. Plac1 ablation resulted in placentomegaly and mild intrauterine growth retardation (IUGR). At E16.5, knockout (KO) and heterozygous (Het) placentae of the Plac1-null allele inherited from the mother (Xm-X) weighed approximately 100% more than wildtype (WT) placentae, whereas the corresponding embryos weighed 7–12% less. Histologically, Plac1 mutants exhibited an expanded spongiotrophoblast layer that invaded the labyrinth. By contrast, Het placentae that inherited the null allele from the father (XXp-) exhibited normal growth and were histologically indistinguishable from WT placentae, consistent with paternal imprinting of Plac1. When examined across gestation, WT and Xm-X placental weights peaked at E16.5 and decreased slightly thereafter. KO placentae (Xm-Xp- and Xm-Y), however, continued to increase in weight after E16.5, consistent with a functional role for the paternal Plac1 allele. Subsequent analysis confirmed that the paternal allele partially escapes complete X-inactivation and thus contributes to placental growth regulation. Additionally, although male Plac1 KO mice can survive, they exhibit decreased viability as a consequence of events occurring late in gestation or shortly after birth. Thus, Plac1 is a paternally imprinted, X-linked gene essential for normal placental and embryonic development.