| Project/Area Number |
17K07429
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Developmental biology
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| Research Institution | National Center for Child Health and Development |
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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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 性分化 / マウス / ゲノム編集 / 遺伝子発言調節 / 遺伝子発現調節 |
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| Outline of Final Research Achievements |
SOX9 is essential for testes formation. Sox9 expression is regulated by an enhancer distal to Sox9 in the genome. In human, the enhancer is located somewhere in 32.5 kb region on 0.6 kb upstream to SOX9. Using mice and murine sequence corresponding to the 32.5 kb region, I identified 711 bp sequence as a responsible sequence. In this research, I tried to unveil the enhancer function of the 711 bp sequence by generation of transgenic mice. On the course of this analysis, another group reported that a fragment in the 711 bp sequence contains enhancer function. Next, I tried to map a responsible sequence in it by generation of mutant mice with microdeletion in the sequence by CRISPR/Cas9 system. The responsible sequence was successfully mapped at 9 bp. I generated mice with single nucleotide substitution in it, and single nucleotide was identified as the responsible sequence. Finally, I estimated a binding factor which binds to the single nucleotide by database search.
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| Academic Significance and Societal Importance of the Research Achievements |
SOX9は精巣分化に必須である。Sox9の発現制御機構を解明することは、性分化の仕組みを理解するだけでなく、性分化疾患の原因解明にも重要である。本研究では、遺伝子改変マウスを作製することで、Sox9遺伝子の発現に重要であることが分かっている711塩基の配列の中から、その中心の役割をする配列を1塩基まで同定した。また、そこに結合する因子を推定できたため、今後その因子がどのようにして711塩基に作用するのかを解明することで、性分化の仕組みや性分化疾患の原因が明らかとなることが期待される。
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