title: Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer.
abstract: 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. 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 p38alpha) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ueshin
authors.forename: Ayako
authors.initials: A
authors.lastname: Isotani
authors.forename: Tomoko
authors.initials: T
authors.lastname: Saito-Fujita
authors.forename: Hisako
authors.initials: H
authors.lastname: Nakashima
authors.forename: Kazushi
authors.initials: K
authors.lastname: Kimura
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Oh-Hora
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mori
authors.forename: Masato
authors.initials: M
authors.lastname: Ogata
authors.forename: Robert G
authors.initials: RG
authors.lastname: Oshima
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D010920:Placenta / Q000502:physiology* / Q000821:virology*; D010922:Placenta Diseases / Q000235:genetics; D011247:Pregnancy; D016019:Survival Analysis; D014161:Transduction, Genetic / Q000379:methods*; D014327:Trophoblasts / Q000821:virology*