Developmental analysis of xenogenic germ cells using blastocyst complementation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02367
• 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 Institute for Physiological Sciences
• Principal Investigator: HIRABAYASHI Masumi 生理学研究所, 行動・代謝分子解析センター, 准教授 (20353435)
• Co-Investigator(Kenkyū-buntansha): 小林 俊寛 生理学研究所, 行動・代謝分子解析センター, 助教 (20587414)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 始原生殖細胞 / 精子 / 卵子 / Prdm14遺伝子 / 生殖細胞欠損 / 異種キメラ / 胚盤胞補完法 / 多能性幹細胞

Outline of Final Research Achievements

Prdm14 gene-deficient rats have been developed to analyze how ES/iPS cells differentiate and develop from primordial germ cells to gametes (sperm cells or oocytes). When blastocysts from these rats were complemented with allogeneic (rat) or xenogeneic (mouse) ES/iPS cells, the presence of ES/iPS cell-derived germ cells was confirmed in the testis or ovary of the resultant chimeric offspring rats. Functional normality of these germ cells was confirmed by the ES/iPS cell-derived offspring production through natural mating (rat-rat allogeneic experimental series) or round spermatid injection (rat-mouse xenogeneic experimental series). Furthermore, the blastocyst complementation was successfully applied with genetically modified allogeneic ES/iPS cells, which could contribute to establish a rapid and efficient system for gene-modified rat production.

Free Research Field

実験動物学、発生工学、生殖工学

Academic Significance and Societal Importance of the Research Achievements

蛍光遺伝子の発現を指標にして始原生殖細胞の動向を追跡できるPrdm14遺伝子欠損ラットを用い、生殖細胞の出現時期とその後の発生過程を明らかにした。本ラットに胚盤胞補完法を適用することでES/iPS細胞由来の生殖細胞を再生できるので、様々な動物種において効率的に遺伝子改変動物を作製できるようになる。効率的な家畜動物の繁殖・生産、絶滅危惧種の保存などへの応用にも繋がりうる成果である。