Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer
Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer
复制标题
DOI：
10.1038/nbt1280
复制
发表时间：
2007-02-01
影响因子：
46.9
通讯作者：
Ikawa, Masahito
中科院分区：
文献类型：
--
作者：
Okada, Yuka;Ueshin, Yuko;Ikawa, Masahito
胎盘功能障碍是妊娠期许多并发症的基础，更好地了解胎盘发育过程中的基因功能可能具有相当大的临床意义。然而，缺乏胎盘特异性基因操作的简便方法阻碍了胎盘器官发生的研究和胎盘功能障碍的治疗。我们之前已经证明，用慢病毒载体转导受精卵会导致两者的转基因表达；胎儿和胎盘（1,2）。在这里，我们报道了胎盘特异性基因通过慢病毒转导小鼠囊胚去除透明带后的整合。所有被分析的胎盘，但没有一个胎儿是转基因的。应用该方法可使缺乏Ets2、Mapk14（也称为p38 α）和Mapk1（也称为Erk2）的小鼠免于胎盘缺陷引起的胚胎致死。在胎盘过程中，Mapk11的异位表达也弥补了Mapk14的缺失。
Placental dysfunction underlies many complications during pregnancy, and better understanding of gene function during placentation could have considerable clinical relevance. However, the lack of a facile method for placenta-specific gene manipulation has hampered investigation of placental organogenesis and the treatment of placental dysfunction. We showed previously that transduction of fertilized mouse eggs with lentiviral vectors leads to transgene expression in both ;the fetus and the placenta(1,2). Here we report placenta-specific gene incorporation by lentiviral transduction of mouse blastocysts after removal of the zona pellucida. All of the placentas analyzed, but none of the fetuses, were transgenic. Application of this method substantially rescued mice deficient in Ets2, Mapk14 ( also known as p38 alpha) and Mapk1 ( also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.