Research abstract

Letter abstract


Nature Biotechnology 25, 233 - 237 (2007)
Published online: 14 January 2007 | doi:10.1038/nbt1280

Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer

Yuka Okada1, Yuko Ueshin1,2, Ayako Isotani1,2, Tomoko Saito-Fujita1, Hisako Nakashima3, Kazushi Kimura3, Akira Mizoguchi3, Masatsugu Oh-hora3, Yoshiko Mori3, Masato Ogata3, Robert G Oshima4, Masaru Okabe1,2 & Masahito Ikawa1

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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 placenta1, 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 p38alpha) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.

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  1. Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  2. Graduate School of Pharmaceutical Sciences, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
  3. School of Medicine, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
  4. The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.

Correspondence to: Masahito Ikawa1 e-mail: ikawa@biken.osaka-u.ac.jp

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