| Project/Area Number |
18K09776
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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 57060:Surgical dentistry-related
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉賀 大午 九州歯科大学, 歯学部, 准教授 (10507784)
中富 満城 九州歯科大学, 歯学部, 講師 (10571771)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Msx1 / 低酸素環境 / 口蓋裂 / フェニトイン / 遺伝環境相互作用 / MSX1 / 低酸素負荷 / 低酸素ストレス / 口蓋突起 / 口蓋発生 |
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| Outline of Final Research Achievements |
This study aimed to clarify whether gene-environment interaction can cause cleft palate. Msx1 heterozygosity in mice (Msx1+/-) was selected as a genetic factor. As an environmental factor, hypoxic stress was induced in pregnant mice by administration of the antiepileptic drug phenytoin (PHT) during palatal development from embryonic day (E) 11 to E14. Embryos were dissected at E13 for histological analysis or at E17 for recording of the palate. PHT administration downregulated cell proliferation in palatal processes in both wild-type and Msx1+/- embryos. Bone morphogenetic protein4 (Bmp4) expression was downregulated in the anterior palatal process of Msx1+/- embryos. Although Msx1+/- embryos do not show cleft palate under normal conditions, PHT administration induced a significantly higher incidence of cleft palate in Msx1+/- embryos compared to wild-type. Our data suggest that cleft palate may occur because of the additive effects of Msx1 heterozygosity and hypoxic stress.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果から、通常の状態ではMsx1遺伝子に変異があったとしても、口蓋裂を発生しないが、胎仔が低酸素環境下におかれた状態にMsx1遺伝子変異が加わると口蓋裂が発生し、野生型より口蓋裂発生率が高いことがわかった。以上のことから、低酸素環境下での細胞増殖抑制とMsx1変異の相加的効果による口蓋裂発生の可能性が示唆された。
遺伝子検査が可能となれば、MSX1 変異がある場合は、妊娠中は環境リスクへの暴露を避けるように指導することで、口蓋裂発生の危険性を下げることが可能になると考えられる。
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