2002 Fiscal Year Final Research Report Summary
Development and electrophysiological analysis of genetically engineered transgenic mice for Brugada syndrome.
| Project/Area Number |
13670685
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NAOMASA Makita Hokkaido University Graduate School of Medicine, Instructor, 大学院・医学研究科, 助手 (00312356)
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| Co-Investigator(Kenkyū-buntansha) |
ITSUO Kodama Research Institute of Environmental Medicine, Nagoya University, Professor, 環境医学研究所, 教授 (30124720)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Brugada syndrome / Transgenic mice / Ventricular fibrillation / Na channel / Mutations |
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| Research Abstract |
Transgenic mice expressing human cardiac Na channel α subunit gene (SCN5A) under the control of myosin heavy chain promoter were developed. Two trains with wild type (WT) SCN5A and a missense mutation T1620M identified in a Brugada syndrome, a subtype of idiopathic ventricular fibrillation. Neither WT nor T1620M mice showed sudden death or ST elevation in right precordial leads characteristic for Brugada syndrome. Na channel blocker Pilsicainide failed to induce ST elevation or ventricular arrhythmias in T1620M, however, programmed electrophysiological studies with double extra stimuli on the right ventricular free wall provoked polymorphic ventricular tachycardia in T1620M but not in WT, suggesting the existence of arrhythmic substrates in the T1620M mice. Since the heart rate and the action potential configuration of mice are far from similar to those of human, further technological improvements such as developing bicistronic Na channel constructs expressing SCN5A and tag proteins or engineering knock-in animals, which in turn providing more suitable model animal to study the pathophysilogical mechanisms underlying the life-threatening disease Brugacla syndrome.
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Research Products
(32 results)
