| Project/Area Number |
15K18810
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Insect science
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| Research Institution | Kyushu University |
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Principal Investigator |
Fujii Tsuguru 九州大学, 農学研究院, 学術研究員 (50507887)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 尿酸 / キサンチン水酸化酵素 / キサンチン酸化酵素 / モリブデン補酵素 / XDH / XO / MoCo / ゲノム編集 / RNA-seq / DNA-seq / CRISPR/Cas9 / 尿酸顆粒 / 卵形成 / モザイク解析 / 次世代シーケンス / 真皮細胞 |
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| Outline of Final Research Achievements |
oel mutants of B. mori exhibit a pleiotropic phenotypic defect, including retarded growth, an extra larval molt, and translucent larval integument owing to a lack of uric acid. We physiologically and genetically characterized oel mutants to elucidate the dual function of oel controlling the endocrine system and uric acid metabolism. Rescue experiments using bovine xanthine oxidase revealed that oel governed the enzymatic activity of xanthine dehydrogenase (XDH), a key enzyme for uric acid synthesis. Phenotypic comparison of oel mutants and other XDH deficient mutants indicated that oel is unrelated to molybdenum cofactor synthesis, which is indispensable for the enzymatic activity of XDH. Moreover, DNA-seq and RNA-seq analysis identified a frameshift mutation in a gene encoding antioxidant protein. Although genes orthologous to the identified gene are present in other organisms, their involvement in uric acid metabolism has not been reported.
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| Academic Significance and Societal Importance of the Research Achievements |
尿酸代謝や内分泌系に異常を示すカイコのoel変異体の遺伝・生理学的な解析により、尿酸代謝の鍵酵素であるキサンチン水酸化酵素(XDH)の活性を支配する新規な遺伝子が同定された。当該遺伝子の機能を解明することにより、尿酸代謝や内分泌系の破綻により害虫を駆除する新技術の開発に繋がる。また、XDHの活性はヒトでは痛風等の病態との関連が知られていることから、XDH活性を標的とした創薬研究の基盤となる。カイコには尿酸代謝に異常を有する突然変異が豊富に存在する。本研究により、カイコは尿酸代謝研究における優れたモデル生物であることが示された。
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