Transgenic primates as research tools: now a reality

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Article

Nature 459, 523-527 (28 May 2009) | doi:10.1038/nature08090; Received 27 September 2008; Accepted 30 April 2009

Generation of transgenic non-human primates with germline transmission

Erika Sasaki¹, Hiroshi Suemizu¹, Akiko Shimada¹, Kisaburo Hanazawa², Ryo Oiwa¹, Michiko Kamioka¹, Ikuo Tomioka^1,3, Yusuke Sotomaru⁵, Reiko Hirakawa^1,3, Tomoo Eto¹, Seiji Shiozawa^1,4, Takuji Maeda^1,4, Mamoru Ito¹, Ryoji Ito¹, Chika Kito¹, Chie Yagihashi¹, Kenji Kawai¹, Hiroyuki Miyoshi⁶, Yoshikuni Tanioka¹, Norikazu Tamaoki¹, Sonoko Habu⁷, Hideyuki Okano⁴ & Tatsuji Nomura¹

1. Central Institute for Experimental Animals, 1430 Nogawa, Miyamae-ku, Kawasaki, Kanagawa 216-0001, Japan
2. Department of Urology, Juntendo University Nerima Hospital 3-1-10 Takanodai, Nerima-ku, Tokyo 177-8521, Japan
3. Center for Integrated Medical Research,
4. Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
5. Natural Science Centre for Basic Research and Development, Hiroshima University 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan
6. Subteam for Manipulation of Cell Fate, RIKEN BioResource Centre, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
7. Department of Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan

Correspondence to: Erika Sasaki¹Hideyuki Okano⁴ Correspondence and requests for materials should be addressed to E.S. (Email: esasaki@ciea.or.jp) or H.O. (Email: hidokano@sc.itc.keio.ac.jp).

Abstract

The common marmoset (Callithrix jacchus) is increasingly attractive for use as a non-human primate animal model in biomedical research. It has a relatively high reproduction rate for a primate, making it potentially suitable for transgenic modification. Although several attempts have been made to produce non-human transgenic primates, transgene expression in the somatic tissues of live infants has not been demonstrated by objective analyses such as polymerase chain reaction with reverse transcription or western blots. Here we show that the injection of a self-inactivating lentiviral vector in sucrose solution into marmoset embryos results in transgenic common marmosets that expressed the transgene in several organs. Notably, we achieved germline transmission of the transgene, and the transgenic offspring developed normally. The successful creation of transgenic marmosets provides a new animal model for human disease that has the great advantage of a close genetic relationship with humans. This model will be valuable to many fields of biomedical research.