Establishment of the chromatin state in gonadal development

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Yuko Katoh-fukui 国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, (非)研究員 (50342639)
• Co-Investigator(Kenkyū-buntansha): 竹内 隆 鳥取大学, 医学部, 教授 (70197268)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: クロマチン / 生殖腺 / 分化 / マウス

Outline of Final Research Achievements

Dynamic chromatin structural transformation occurs in the differentiated cell nucleus. In this study, we focused on the Polycomb Group (PcG) member, Cbx2 and the chromatin component Jarid2 (Jumonji), which is known to associate with PcG in ES cells. In order to verify the Jarid2 flox allele, we deleted floxed exon three regions by using germ-line active Cre. The obtained Jarid2 deficient embryo confirmed edema, septal defect of the heart, and hypoplasia of the liver, similar to the phenotypes observed in previously reported gene-trap mice. In addition, we found an unreported dysplasia of the urogenital regions and retinal coloboma. Furthermore, mutation analysis of these factors in disorders of sex development (DSD) was performed.

Free Research Field

発生遺伝

Academic Significance and Societal Importance of the Research Achievements

発生中の多様な時期に、多様な組織で機能を果たすクロマチン構成因子のより詳細な解析のために、Jarid2 flox alleleマウスを用いた組織特異的機能解析が可能であることが明らかになった。DSDのみならず様々な小児疾患原因因子あるいはリスク因子としてクロマチン構成因子変異が検討されるべきであることを示した。