Generation of transgenic monkey with tetracyclin-inducible gene expression system for neurodegenerative disease model.

• Project/Area Number: 26870884
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science; Nerve anatomy/Neuropathology
• Research Institution: Shinshu University
• Principal Investigator: TOMIOKA Ikuo 信州大学, 学術研究院農学系, 助教 (30528196)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Yoshitaka 大阪大学, 医学部, 教授 (60335354) ; SEKI Kazuhiko 国立精神・神経医療研究センター, 部長 (00226630)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: マーモセット / トランスジェニック / TETシステム / 遺伝子改変 / 疾患モデル / 神経変性疾患 / ポリグルタミン病

Outline of Final Research Achievements

Artificially controllable transgene expression system is indispensable tool for production of various disease model animals to precisely mimic human disease states. In the present study, we successfully generated transgenic marmoset line with tetracyclin-inducible gene expression system for neurodegenerative disease model. Mutant human ataxin 3 gene with 120 CAG repeats controlled by tetracycline-inducible system was introduced into marmoset embryos via lentiviral transduction. A total of seven live offspring were obtained. They and their fibroblast cells treated doxycycline revealed inducible transgene expression compared to before treatment. Moreover, a total of five second-generation (F1) offspring were obtained from founder marmosets and one was transgenic, showing successful germline transmission of transgene. In conclusion, the present study generated transgenic marmoset line having mutant human ataxin 3 gene controlled by tetracycline-inducible system.

Research Products

• [Journal Article] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms. (2017)
  • Author(s): Tomioka I, Ishibashi H, Minakawa EN, Motohashi HH, Takayama O, Saito Y, Popiel HA, Puentes S, Owari K, Nakatani T, Nogami N, Yamamoto K, Noguchi S, Yonekawa T, Tanaka Y, Fujita N, Suzuki H, Kikuchi H, Aizawa S, Nagano S, Yamada D, Nishino I, Ichinohe N, Wada K, Kohsaka S, Nagai Y, Seki K.
  • Journal Title: eNeuro Volume: 4 Issue: 2 Pages: 0250-56
  • DOI: 10.1523/eneuro.0250-16.2017
  • NAID: 120007100051
  • Peer Reviewed / Open Access
• [Journal Article] 非ヒト霊長類における発生工学の歴史 (2016)
  • Author(s): 富岡郁夫
  • Journal Title: 信州大学農学部紀要 Volume: 52 Pages: 9-15
  • NAID: 120007101368
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Generation of transgenic marmoset line with polyglutamine disease and behavioral phenotyping. (2016)
  • Author(s): K Owari, N Nogami, T Nakatani, M Koizumi, H Ishibashi, Y Nagai, I Tomioka, K Seki.
  • Organizer: Society for Neuroscience 46th annual meeting
  • Place of Presentation: San Diego convention center, San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] マーモセットにおける遺伝子組換え動物作製の実際とその可能性について (2016)
  • Author(s): 富岡郁夫
  • Organizer: 第50回日本実験動物技術者協会総会
  • Place of Presentation: ウェスタ川越、川越市、埼玉県
  • Year and Date: 2016-09-29
  • Invited
• [Presentation] SCA3モデルマーモセットの作出 (2016)
  • Author(s): 富岡郁夫
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸コンベンションセンター、神戸市、兵庫県
  • Year and Date: 2016-05-20
  • Invited
• [Presentation] ポリグルタミン病マーモセットの作出 (2015)
  • Author(s): 富岡郁夫
  • Organizer: 第36回 国立精神・神経医療研究センター 神経研究所 研究発表会
  • Place of Presentation: 東京都小平市 国立精神・神経医療研究センター
  • Year and Date: 2015-03-05 – 2015-03-06