| Project/Area Number |
18K19847
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 63:Environmental analyses and evaluation and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
池中 良徳 北海道大学, 獣医学研究院, 准教授 (40543509)
中山 翔太 北海道大学, 獣医学研究院, 助教 (90647629)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 殺鼠剤 / シトクロムP450 / ビタミンKエポキシド還元酵素 / 野生齧歯類 / ラット / 抵抗性 |
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| Outline of Final Research Achievements |
Currently, secondary damage to birds of prey from rodenticides is frequently occurring. Therefore, no effective and safe control measures exist for rodenticide-resistant rats. This is due to the lack of research on resistance acquisition mechanisms and the lack of methods for assessing susceptibility in wildlife. The purpose of this study was to elucidate the causes of the acquisition of rodenticide resistance and to obtain data that will contribute to the development of rodenticides and their conservation to non-target species. This study demonstrated that mutations in the binding pocket and within the binding pocket of vitamin K epoxide reductase contribute to the acquisition of resistance in wild rodents as a cause of rodenticide resistance, and revealed a new mechanism of resistance acquisition through enhanced NADPH production and subsequent activation of rodenticide metabolism by cytochrome P450.
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| Academic Significance and Societal Importance of the Research Achievements |
国内で発生している野生齧歯類の殺鼠剤抵抗性の原因について、ビタミンKエポキシド還元酵素（VKOR)と殺鼠剤との親和性の低下のほか、電子伝達系の変化によるシトクロムP450の活性上昇という新しいメカニズムを提唱した。現在、世界中で殺鼠剤の非対象生物への毒性が問題となっているが、本研究は新規殺鼠剤の新規開発にも資するものであり、また、非対象生物のリスクアセスメントのクライテリアにも貢献することができる。
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