| Project/Area Number |
18K16492
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
Shinjo Takeaki 奈良県立医科大学, 麻酔科学教室, 助教 (70624914)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 疼痛 / マクロファージ / Shorting nexin / 疼痛関連因子 / トランスジェニックマウス |
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| Outline of Final Research Achievements |
Pain significantly reduces quality of life in various diseases. The cellular and molecular mechanisms of pain remain largely unknown.We noticed that pain responses were extremely reduced in a bacterial artificial chromosome-transgenic (BAC-TG) mice. Since this TG mice harbors a BAC transgene, we first speculated that exogenous genes in the BAC may modulate pain behaviors. The exogenous gene expressions, however, were indistinguishable from those in naive mice. Based on a next hypothesis that the large transgene might affect endogenous gene expression and thereby influence pain behaviors, we performed forward genetic screening using next generation sequencing.The BAC transgene was inserted into chromosome 8 and three genes in the vicinity of the insertion site were almost knocked out. Whether these genes are involved in pain sensing mechanisms is an open question. To elucidate the roles of the candidates in pain behaviors, we investigated knockout (KO) and conditional KO mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、痛みを感じないTGマウスを使用できることが最大の特徴である。一般的な遺伝子の機能解析手法としては、ノックアウト(KO)など遺伝子を操作してその表現型を調べる逆遺伝学が主要な方法であるが、本研究で用いた手法は、変異マウスを用いて表現型からその原因となる遺伝子を探りあてる順遺伝学である。詳細な検討の結果、疼痛鈍麻の表現型を示すTGマウスは、外来遺伝子が8番染色体に挿入され、挿入部位近傍の３つの遺伝子制御が破綻していることを明らかにした。興味深いのは、これらの候補因子は全てこれまで報告のある疼痛関連因子ではないことである。新規疼痛関連遺伝子を同定できたことは学術的に意義あるものである。
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