The Role of PLAC1 in Placental Growth

描述(申请人提供)：Placi是一种最近描述的X连锁 一种由滋养层细胞独占表达的基因 胎盘组织。胎盘在胎盘发育中的一个重要作用是 由其组织特异性和时间表达模式强烈提示。 胎儿发育迟缓的表型强化了这一观点。 与PLAC1所在区域的X染色体缺失相关。 此外，独立研究还表明，X的这一区域 染色体上含有对胎盘生长有重要作用的基因(S)。计算机辅助 对X染色体这一区域的分析表明，Placi是领先的 与这些相关的胎盘异常的候选基因 基因缺失。PLAC1与透明带蛋白序列同源性 3(ZP3)提示它可能参与特定的细胞相互作用 在母胎界面，可能起到细胞表面受体的作用。 从整体上看，这些观察结果强烈表明PLAC1编码一个 胎盘特异性胞外蛋白对哺乳动物非常重要 繁殖。因此，它很可能成为一个重要的标志 胎盘和胎儿的健康。拟议中的研究将开发一种小鼠 Placl基因敲除模型，以确定其在胎盘发育中的作用。 此外，PLAC1的表达将作为滋养层细胞的功能进行研究 分化将在正常的人滋养层细胞中进行研究。最后，人类 PLAC1蛋白的表达、鉴定及其潜在的受体 功能研究。这些研究将为机理提供新的见解。 对胎盘的生长和功能很重要，并将成为未来的基础 旨在确定PLAC1在细胞水平上的作用的研究。

DESCRIPTION (Provided by Applicant): PLACI is a recently described X-linked gene that is expressed exclusively by cells of trophoblastic origin in placental tissue. A significant role for PLACI in placental development is strongly suggested by its tissue-specific and temporal pattern of expression. This suggestion is strengthened by a fetal growth retardation phenotype associated with X chromosome deletions in the region to which PLAC1 maps. Additional, independent studies have also suggested that this region of the X chromosome contains gene(s) important in placental growth. Computer assisted analysis of this region of the X chromosome suggests PLACI is the leading candidate gene responsible for placental abnormalities associated with these gene deletions. PLAC1 shares sequence homology with the zona pellucida protein 3 (ZP3) suggesting that it may be involved in specific cellular interactions at the maternal-fetal interface, possibly acting as a cell surface receptor. Viewed collectively, these observations strongly suggest that PLAC1 encodes a placenta-specific extracellular protein of major importance to mammalian reproduction. It is likely, therefore, to serve as an important marker for placental and fetal well-being. The proposed studies will develop a mouse Placl knockout model to define its role in placental development. Additionally, PLAC1 expression will be studied as a function of trophoblast differentiation will be studied in normal human trophoblasts. Finally, human PLAC1 protein will be expressed, characterized, and its potential receptor function studied. These studies will provide new insights into mechanism important to placental growth and function, and will form the basis for future studies aimed at defining the role of PLAC1 at the cellular level.