2018 Fiscal Year Final Research Report
A trial for establishment of the cell banks as the models of malignant hyperthemia
| Project/Area Number |
16K08917
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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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| Research Field |
Applied pharmacology
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小山田 英人 昭和大学, 医学部, 講師 (50266160)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 悪性高熱症 / リアノジン受容体 / 遺伝子診断 / 疾患モデル / 全身麻酔薬 |
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| Outline of Final Research Achievements |
We established the simplified method for getting the cell lines to express the genetic variants of the type 1 ryanodine receptor (RyR1, Ca2+-releasing channel) in the case reports of malignant hyperthermia (MH) patients, and to develop in effectively to determine the association to lead to preoperative genetic diagnosis of the MH between the mutations in the RyR1 gene and change of the drug susceptibility. Furthermore, we analyzed the presence of the change in the drug susceptibility of the RyR1 expressed cells due to the RyR1 mutation sites by combining it with a Ca2+ imaging system. We showed that some RyR1 mutations associated with the MH patients in the case reports strongly related with the increment of the drug sensitivity giving the evidence of the MH genetic diagnosis and it could be MH disease model cells for drug discovery of a novel general anesthetics.
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| Free Research Field |
医歯薬学
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| Academic Significance and Societal Importance of the Research Achievements |
これらの研究成果により、国内外で、MH発症に関わるRyR1遺伝子変異部位が明らかにされて術前のMH遺伝子診断の根拠となり得る研究結果を示すと共に、これらのMH型RyR1変異体を発現する細胞をMH疾患モデルとしてより安全な新たな全身麻酔薬の開発に利用することにより安全な医療行為の発展に貢献できるものと期待される。本研究課題で使用したカセット構造化した野生型とMH型RyR1変異体cDNA、並びにその発現細胞株は、国内外の研究者の要望があれば提供することができるようになった。今後は、多くの研究者が簡易に目的とするRyR1変異体の作製と発現する細胞株の樹立も可能で、新たな研究の展開も期待される。
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