2022 Fiscal Year Final Research Report

Development of novel techniques for generation of genome engineering marmosets

Research Project

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Project/Area Number	20H03177
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 42040:Laboratory animal science-related
Research Institution	National Center for Child Health and Development (2022) Central Institute for Experimental Animals (2020-2021)
Principal Investigator	Watanabe Toshiaki 国立研究開発法人国立成育医療研究センター, 細胞医療研究部, 専門職 (40715405)
Co-Investigator(Kenkyū-buntansha)	山海直国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所霊長類医科学研究センター, 再雇用職員 (80300937)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	マーモセット / 生殖細胞 / 精子幹細胞 / 初期胚 / ノックイン / 移植前選抜
Outline of Final Research Achievements	Genetically modified primates are very useful for research understanding primate-specific mechanisms and phenomena. Since primates and mice differ greatly, techniques for the generation of genetically modified primates need to be adapted to primates. Currently, in marmosets, only simple knockout or transgenic animals can be generated. In this study, I developed two novel techniques for the generation of genetically modified marmosets. First, I developed a method to select embryos with the desired reporter gene knock-in before the transplantation. Using NanoLuc, which produces highly sensitive chemiluminescence, knock-in embryos were selected before transplantation. The second is the development of host animals for germline transplantation. By using the HSV-TK system, we developed a more 3R-compatible method than the current method. The results of this study will provide a basis for making various types of genetically engineered animals in a way that is suitable for primates.
Free Research Field	霊長類生殖生物学
Academic Significance and Societal Importance of the Research Achievements	非ヒト霊長類を使った研究は、マウスでは明らかにすることができない霊長類に特有なメカニズム・現象を理解する上で必要である。遺伝子改変霊長類はそのような研究を進める上でたいへん役に立つ。霊長類とマウスでは飼育の費用、得られる産子の数、妊娠・性成熟期間など大きく異なる。そのため、発生工学技術に関してもマウスとは異なる霊長類に適した戦略が必要になる。本研究で得られた成果は、これまで知られていなかった霊長類特有の生物学的知見を産み出すとともに病態モデルの作製を通した医学の発展に貢献する。