Identification of the regulatory mechanism of human SOX9 expression using mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06678
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Takada Shuji 国立研究開発法人国立成育医療研究センター, システム発生・再生医学研究部, 部長 (20382856)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マウス / Sox9 / 性分化 / 性決定 / エンハンサー

Outline of Final Research Achievements

The enhancers in the XYSR and XXSR regions are critical for SOX9 expression, which functions in the early stages of sex determination, based on analysis of human cases of disorders of sex development. In this study, mice in which a mouse enhancer in the XYSR region was replaced with a human one were analyzed. The results showed that the enhancers did not function by substitution, suggesting that species differences in the enhancer, SRY protein, and/or Sox9 promoter would affect the function of the enhancer. Generation of mice with those substituted with human sequences were attempted, but it was not completed. The mice with mutations in the XXSR region was generated. XY female mice were identified with incomplete penetrance. Sequence analysis was performed to determine this mutation, but was not completed.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

ヒトとマウスのXYSR領域のエンハンサーはマウス個体内では互換性がないことから、エンハンサーが機能する際には種差の影響のある何かが関与することが示された。XXSR領域については、マウスが変異を有していても雄になる個体と雌になる個体がいたことから、遺伝的背景が影響するモディファイヤーの関与が示された。今後モディファイヤーの同定により、XXSRの機能の解明が可能になると考えられる。