Screening of germ cell related genes and generation of disease model animals

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21504
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Ishiguro Kei-ichiro 熊本大学, 発生医学研究所, 教授 (30508114)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 減数分裂 / 不妊

Outline of Final Research Achievements

In order to understand causal relationship between human infertility and meiosis, we have studied whole genome sequence of 11 Primary ovarian insufficiency (POI) patients by exome analysis. By comparing the genome sequence of POI and meiotic genes that we previously identified, we found heterozygous mutations in meiotic genes. This is yet to be evaluated by examining phenotypes in model animals that mimic the mutation. Further, we newly identified a gene that plays essential roles in meiosis. Disruption of FBXO47 shows severe impact on homologous chromosome synapsis and meiotic recombination, leading to male infertility. Notably, in the absence of FBXO47, although once homologous chromosomes are synapsed, the synaptonemal complex is precociously disassembled before completion of meiosis. Our study will shed light on the understanding of causal relationship between human infertility and meiosis.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は疾患モデル動物を用いた研究により検証されたものですが、FBXO47遺伝子はヒトにも存在することがわかりました。ヒトに見られる不妊症は原因が不明とされる症例が多く、今回の発見は、特に卵巣不全や無精子症や精子形成不全を示す不妊症の病態の解明に資するものと期待されます。また、MEIOSINの指令下で働くことが予想される他の機能未解明の遺伝子の働きについてはまだ十分に解明されていません。今後、卵子・精子の形成過程におけるこれら他の遺伝子の働きも同時に解明することで、生殖医療に大いに貢献できると期待されます。