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13 October 2017 Generation of transgenic marmosets using a tetracyclin-inducible transgene expression system as a neurodegenerative disease model
Ikuo Tomioka, Naotake Nogami, Terumi Nakatani, Kensuke Owari, Naoko Fujita, Hideyuki Motohashi, Osamu Takayama, Kentaro Takae, Yoshitaka Nagai, Kazuhiko Seki
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Abstract

Controllable transgene expression systems are indispensable tools for the production of animal models of disease to investigate protein functions at defined periods. However, in nonhuman primates that share genetic, physiological, and morphological similarities with humans, genetic modification techniques have not been well established; therefore, the establishment of novel transgenic models with controllable transgene expression systems will be valuable tools to understand pathological mechanism of human disease. In the present study, we successfully generated transgenic marmosets using a tetracyclin-inducible transgene expression (tet-on) system as a neurodegenerative disease model. The mutant human ataxin 3 gene controlled by the tet-on system was introduced into marmoset embryos via lentiviral transduction, and 34 transgene-introduced embryos were transferred into the uteri of surrogate mothers. Seven live offspring (TET1–7) were obtained, of which four were transgenic. Fibroblasts from TET1 and 3 revealed that inducible transgene expression had occurred after treatment with 10 μg/mL of doxycycline, while treatment with doxycycline via drinking water resulted in 1.7- to 1.8-fold inducible transgene expression compared with before treatment. One transgenic second-generation offspring (TET3-3) was obtained from TET3, and doxycycline-inducible transgene expression in its fibroblasts showed that TET3-3 maintained a high transgene expression level that matched its parent. In conclusion, we established a novel transgenic marmoset line carrying the mutant human ataxin 3 gene controlled by the tet-on system. The development of nonhuman primate models with controllable transgene expression systems will be useful for the identification of disease biomarkers and evaluation of the efficacy and metabolic profiles of therapeutic candidates.

Summary Sentence

Transgenic marmoset generation using the tetracyclin-inducible transgene expression system provides a model for human neurodegenerative disease.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Ikuo Tomioka, Naotake Nogami, Terumi Nakatani, Kensuke Owari, Naoko Fujita, Hideyuki Motohashi, Osamu Takayama, Kentaro Takae, Yoshitaka Nagai, and Kazuhiko Seki "Generation of transgenic marmosets using a tetracyclin-inducible transgene expression system as a neurodegenerative disease model," Biology of Reproduction 97(5), 772-780, (13 October 2017). https://doi.org/10.1093/biolre/iox129
Received: 13 July 2017; Accepted: 12 October 2017; Published: 13 October 2017
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KEYWORDS
gene regulation
intracytoplasmic sperm injection (ICSI)
Primates
transgenesis
transgenic/knockout model
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