Elucidation of the pathophysiology and etiology of congenital long QT syndrome type 6 by myocardial cell screening and iPS technology
| Project/Area Number |
17K08539
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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 |
General physiology
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
李 佩俐 鳥取大学, 医学(系)研究科(研究院), 助教 (40464292)
池田 信人 鳥取大学, 医学(系)研究科(研究院), 助教 (50620316)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 疾患iPS細胞 / QT延長症候群 / 蛍光タンパク質 / ペースメーカ細胞 / 心室筋 / 先天性QT延長症候群 / MIRP1 / HCN4 / MLC2v / 洞結節ペースメーカ / イオンチャネル / 可視化 / ヒトiPS 細胞 / 心筋 / ゲノム編集 / 心室筋細胞 / MiRP1 / 再生医学 / 生理学 / バイオテクノロジー / iPS細胞 |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the etiology and pathophysiology of congenital long QT syndrome type 6 (LQTS6). Using patient-derived disease iPS cells, we succeeded in establishing a cell line in which sinus node pacemaker cells and ventricular cells having the same MiRP1 gene mutation as the patient can be individually visualized by fluorescent proteins. The fractionated cardiomyocytes showed the specific maker expression and electrophysiological characteristics of sinus node pacemakers or ventricular muscle cells. Although we have not reached a detailed analysis of the etiology and pathophysiology, we would like to proceed with the elucidation of the pathophysiology because cardiomyocyte with the same property of patient can be prepared by using the established LQTS6 iPS cell. At the same time, we have succeeded in improving the method for inducing myocardial differentiation and developing a new visualization-selective collection method for sinus node pacemaker cells.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性QT延長症候群タイプ6（LQTS6）の病因・病態解明のために必要な洞結節ペースメーカ細胞と心室筋細胞を、選択的に可視化－選別採取できるLQTS6疾患iPS細胞株の作製に成功している。この細胞株を使い電気生理学的解析等を詳細に進めることができれば、LQTS6に特有な徐脈とQT延長という2つの異なった症状を生み出す分子メカニズムの詳細に迫ることができると考えている。また、原因遺伝子MiRP1について、患者と同等の変異を持つこれらの細胞は、LQTS6患者の診断、薬剤スクリーニングを通じて、病気の治療のみならず、心臓の拍動制御システムの解明にも貢献すると期待している。
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Report
(6 results)
Research Products
(28 results)
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[Journal Article] Inhibitory effects of class I antiarrhythmic agents on Na+ and Ca2+ currents of human iPS cell-derived cardiomyocytes.2019
Author(s)
Yonemizu S, Masuda K, Kurata Y, Notsu T, Higashi Y, Fukumura K, Li P, Ninomiya H, Miake J, Tsuneto M, Shirayoshi Y, Hisatome I.
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Journal Title
Regen Ther.
Volume: 10
Pages: 104-111
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells2017
Author(s)
Onohara, Takeshi; Hisatome, Ichiro; Kurata, Yasutaka; Li, Peili; Notsu, Tomomi; Morikawa, Kumi; Otani, Naoyuki; Yoshida, Akio; Iitsuka, Kazuhiko; Kato, Masaru; Miake, Junichiro; Ninomiya, Haruaki; Higaki, Katsumi; Shirayoshi, Yasuaki; Nishihara, Takashi; Itoh, Toshiyuki; Nakamura, Yoshinobu; Nishimura, Motonobu
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Journal Title
J. Arrhythmia,
Volume: 32
Issue: 3
Pages: 226-233
DOI
Related Report
Peer Reviewed / Open Access
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