| 研究課題/領域番号 |
23K05601
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分42040:実験動物学関連
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| 研究機関 | 名古屋市立大学 |
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研究代表者 |
シャウキ ホッサム 名古屋市立大学, 医薬学総合研究院(医学), 助教 (70829738)
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| 研究分担者 |
大石 久史 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30375513)
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2025年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2024年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
2023年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
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| キーワード | Wolffian duct / Anomalies / MycN / reproductive truct / retinoic acid / mycn |
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| 研究開始時の研究の概要 |
Retinoic acid signaling were found to induce the reproductive tract development. We found a patient with MYCN mutation that turn it to be constitutive active. By generating mouse model similar to that patient, the mouse will be analyzed whether the reproductive tract malformation was developed. We also examine that increasing MYCN expression inhibit retinoic acid signaling in the reproductive development and that might cause a genital malformation. In our proposal, we aim to identify the detailed mechanism of MYCN/RA axis during the development of the reproductive tract.
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| 研究実績の概要 |
Congenital anomalies of the reproductive tract are common and often stem from developmental errors in the Wolffian duct in both sexes. Mutations or inhibition of retinoic acid receptors can disrupt Wolffian duct development, leading to genital malformations in males and females. Overexpression of MYCN inhibits retinoic acid signaling, potentially contributing to these anomalies. We investigated a mouse model of constitutive active MYCN (MYCN-T58M) mimicking a human patient mutation. This year, I completed the analysis of the adult mutant MYCN mouse genital tracts. The male and female mice exhibit infertility. Female mice showed imperforate vagina, uterine hydrometria, and blind-ended uterine horns, while males exhibited convoluted vas deferens and abnormal seminal vesicles. These phenomena suggest a shared congenital abnormality in reproductive tract development during embryogenesis between males and females.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
Half of the project has been completed
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| 今後の研究の推進方策 |
We will examine the localization of MYCN expression during embryogenesis and use histological and molecular techniques to identify the time point where the developmental abnormality started. Wolffian duct development will be deeply examined through the current project to clarify the genetic basis of reproductive tract development.
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