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

Yuka Okada; Yuko Ueshin; Ayako Isotani; Tomoko Saito-Fujita; Hisako Nakashima; Kazushi Kimura; Akira Mizoguchi; Masatsugu Oh-Hora; Yoshiko Mori; Masato Ogata; Robert G. Oshima; Masaru Okabe; Masahito Ikawa

doi:10.1038/nbt1280

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

Yuka Okada, Yuko Ueshin, Ayako Isotani, Tomoko Saito-Fujita, Hisako Nakashima, Kazushi Kimura, Akira Mizoguchi, Masatsugu Oh-Hora, Yoshiko Mori, Masato Ogata, Robert G. Oshima, Masaru Okabe, Masahito Ikawa

Research output: Contribution to journal › Article › peer-review

86 Citations (Scopus)

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 p38α) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.

Original language	English
Pages (from-to)	233-237
Number of pages	5
Journal	Nature Biotechnology
Volume	25
Issue number	2
DOIs	https://doi.org/10.1038/nbt1280
Publication status	Published - Feb 2007

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

Access to Document

10.1038/nbt1280

Cite this

@article{de868339f4e04fdd95bff4f98fc480e2,

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 p38α) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.",

author = "Yuka Okada and Yuko Ueshin and Ayako Isotani and Tomoko Saito-Fujita and Hisako Nakashima and Kazushi Kimura and Akira Mizoguchi and Masatsugu Oh-Hora and Yoshiko Mori and Masato Ogata and Oshima, {Robert G.} and Masaru Okabe and Masahito Ikawa",

note = "Funding Information: We thank H.A. Popiel for critical reading of the manuscript, and Y. Maruyama, A. Kawai, Y. Esaki, M. Tanaka and Y. Koreeda for technical assistance. Rat anti-GFP antibody was kindly provided by Fujita of Mitsubishi-Kasei Institute of Life Sciences. This research was supported in part by Uehara Memorial Foundation, Japan Chemical Industry Association (JCIA), and MEXT of Japan.",

year = "2007",

month = feb,

doi = "10.1038/nbt1280",

language = "English",

volume = "25",

pages = "233--237",

journal = "Bio/Technology",

issn = "1087-0156",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer

AU - Okada, Yuka

AU - Ueshin, Yuko

AU - Isotani, Ayako

AU - Saito-Fujita, Tomoko

AU - Nakashima, Hisako

AU - Kimura, Kazushi

AU - Mizoguchi, Akira

AU - Oh-Hora, Masatsugu

AU - Mori, Yoshiko

AU - Ogata, Masato

AU - Oshima, Robert G.

AU - Okabe, Masaru

AU - Ikawa, Masahito

N1 - Funding Information: We thank H.A. Popiel for critical reading of the manuscript, and Y. Maruyama, A. Kawai, Y. Esaki, M. Tanaka and Y. Koreeda for technical assistance. Rat anti-GFP antibody was kindly provided by Fujita of Mitsubishi-Kasei Institute of Life Sciences. This research was supported in part by Uehara Memorial Foundation, Japan Chemical Industry Association (JCIA), and MEXT of Japan.

PY - 2007/2

Y1 - 2007/2

N2 - 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 p38α) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.

AB - 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 p38α) and Mapk1 (also known as Erk2) from embryonic lethality caused by placental defects. Ectopic expression of Mapk11 also complemented Mapk14 deficiency during placentation.

UR - http://www.scopus.com/inward/record.url?scp=33846871665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846871665&partnerID=8YFLogxK

U2 - 10.1038/nbt1280

DO - 10.1038/nbt1280

M3 - Article

C2 - 17220877

AN - SCOPUS:33846871665

VL - 25

SP - 233

EP - 237

JO - Bio/Technology

JF - Bio/Technology

SN - 1087-0156

IS - 2

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this