Rodriguez Clara I, Cheng Jr-Gang, Liu Linda, Stewart Colin L
Cancer and Developmental Biology Laboratory, National Cancer Institute, Division of Basic Science, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
Endocrinology. 2004 Mar;145(3):1410-8. doi: 10.1210/en.2003-1361. Epub 2003 Dec 4.
Embryo implantation is a required step in the reproduction of all mammals. In mice, a transient rise in the uterine expression of leukemia inhibitory factor (LIF) occurs on d 4 of pregnancy and is essential for embryo implantation. However, which genes are regulated by LIF in the uterus at implantation has not been determined. We performed a subtractive hybridization assay between luminal epithelial (LE) mRNAs from d 3 and 4 of pregnancy to find genes up-regulated on d 4 and which would be potentially regulated by LIF. One candidate, Coch-5b2, was up-regulated on the day of implantation. Coch mRNA localized to the LE of wild-type mice and was not detected in uteri from Lif-deficient mice. Treatment of LE with LIF, both in vitro and in vivo, resulted in the up-regulation of Coch. Coch is also highly expressed in other tissues, including the spleen and inner ear, but only in the uterus is Coch expression regulated by LIF. Mice were derived in which Coch was either deleted or tagged with a LacZ reporter. In mice carrying the tagged Coch gene, expression of Coch was detected in the LE and also at the site of embryo implantation. However, mice in which the Coch gene was deleted were normal, showing no overt defects in their reproduction. Although loss of Coch expression is not essential to reproduction in mice, it may serve as a useful marker for assessing the state of uterine receptivity in response to LIF at the onset of implantation.
胚胎着床是所有哺乳动物繁殖过程中的一个必要步骤。在小鼠中，妊娠第4天时子宫中白血病抑制因子（LIF）的表达会短暂升高，这对胚胎着床至关重要。然而，着床时子宫中哪些基因受LIF调控尚未确定。我们对妊娠第3天和第4天的腔上皮（LE）mRNA进行了消减杂交分析，以寻找在第4天上调且可能受LIF调控的基因。一个候选基因Coch-5b2在着床当天上调。Coch mRNA定位于野生型小鼠的LE中，在Lif基因缺陷小鼠的子宫中未检测到。在体外和体内用LIF处理LE，都会导致Coch上调。Coch在包括脾脏和内耳在内的其他组织中也高度表达，但只有在子宫中Coch的表达受LIF调控。构建了Coch基因被删除或用LacZ报告基因标记的小鼠。在携带标记Coch基因的小鼠中，在LE以及胚胎着床部位均检测到Coch的表达。然而，Coch基因被删除的小鼠是正常的，其繁殖过程中没有明显缺陷。虽然Coch表达的缺失对小鼠繁殖并非必不可少，但它可能作为评估着床开始时子宫对LIF反应的子宫接受状态的有用标记。
