Development of MODY5 model mouse using blastocyst complementation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Central Institute for Experimental Animals
• Principal Investigator: Hashimoto Haruo 公益財団法人実験動物中央研究所, 教育・研修室, 研究員 (30353478)
• Co-Investigator(Kenkyū-buntansha): 外丸 祐介 広島大学, 自然科学研究支援開発センター, 教授 (90309352)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胚盤胞補完法 / マウス / MODY2 / MODY5 / ES細胞

Outline of Final Research Achievements

The purpose of this study was to generate a model mouse of Maturity-onset diabetes mellitus of the young type5; MODY5), which is an intractable disease, by using the blastocyst complementation method.Therefore, this time, ES cells (shRNA-ES cells) expressing shRNA for the HNF-1β gene were injected into blastocyst stage eggs of pancreatic and kidney-deficient mice to prepare a chimera.
Asthe results, the chimeric mice produced showed diabetes. From these results, it was shown that the blastocyst complementation method using diseased ES / iPS cells (donor cells) reflects the characteristics of donor cells in the pancreas.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

疾患ES/iPS細胞(ドナー細胞)を用いた胚盤胞補完法は、膵臓ではドナー細胞の特性を反映することが示された。この結果は、ヒトの疾患iPS細胞を用いた場合でも、マウスで個人の膵臓疾患の特性を再現できるものと期待される。
今回、腎臓ではキメラが作製できなかったが、キメラ作製効率の向上により様々な臓器でのヒト化マウスを可能にすると思われる。