The challenge to generate tetraploid mice that can be bred cumulatively

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19237
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: Gunma University
• Principal Investigator: Horii Takuro 群馬大学, 生体調節研究所, 准教授 (00361387)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 4倍体

Outline of Final Research Achievements

Tetraploid mammals are rarely born because they are lethal early in development. We discovered that a p53-dependent checkpoint exists in early development and published that disruption of p53 function dramatically improves the developmental potential of tetraploid embryos (Sci Rep 2015). In this study, disrupting the function of p53 and cyclophilin D (CypD), a component of the Mitochondrial permeability transition pore, successfully increased the viability of tetraploid cells in late gestation. On the other hand, inhibition of p53 and CypD function did not result in the formation of gametes (spermatozoa) of tetraploid origin.

Free Research Field

発生工学

Academic Significance and Societal Importance of the Research Achievements

本研究により、将来的に哺乳類で初めての４倍体由来の配偶子を作出、さらには4倍体動物の累代繁殖につなげることができる。脊椎動物は今日までに2回の全ゲノム倍加（WGD）を繰り返すことで進化してきた。本来ゲノムが倍加することは表現型バリエーションを持たせ、環境変化に適用しやすくなったり、ある染色体がダメージを受けても、他の染色体で代用できたりと、メリットは多いはずである。一方、なぜ下等な両生類は4倍体発生でき、配偶子形成し、子孫を残すことができるのに、高等な哺乳類は4倍体発生も配偶子形成もできなくなってしまったのか、その進化的意義に近づくことができる。