| Project/Area Number |
23K05601
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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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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2024: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2023: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Wolffian duct / Anomalies / MycN / reproductive truct / retinoic acid / mycn |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Half of the project has been completed
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| Strategy for Future Research Activity |
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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