Elucidation of the pathophysiology and etiology of congenital long QT syndrome type 6 by myocardial cell screening and iPS technology

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K08539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Tottori University
• Principal Investigator: SHIRAYOSHI Yasuaki 鳥取大学, 医学部, 准教授 (90249946)
• 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)
• Project Period (FY): 2017-04-01 – 2022-03-31
• 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

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.

Free Research Field

発生生物学

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。