2024.04.18
Establishing a Novel Inherited Arrhythmia Model Mouse Causing Sudden Cardiac Death at Young Age
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Inherited arrhythmias, a serious disorders caused by genetic abnormalities in ion channels and related molecules that regulate cardiomyocyte electrical activity can lead to fatal arrhythmias and sudden cardiac death. Although significant progress has been made in identifying causative molecules and mechanisms, allowing the development of various therapies, including antiarrhythmic drugs, radiofrequency catheter ablation, and implantable cardioverter-defibrillators, a fundamental treatment remains elusive. Thus, there is a pressing need to develop more effective treatment and prevention methods, as well as disease models that can aid in advancing such strategies.
To investigate the pathogenesis of inherited arrhythmias, which are a major cause of sudden cardiac death among young individuals, researchers conducted electrocardiographic screening within a large-scale mouse library with random genetic mutations. They successfully established a mouse pedigree exhibiting inherited arrhythmias that spontaneously leads to lethal arrhythmias. Further genetic analysis identified the causative gene as a novel missense mutation in ryanodine receptor 2 (RyR2: p.I4093V), crucial for regulating intracellular calcium essential for cardiomyocyte contraction. This mouse model, which exhibits severe symptoms of age-related cardiac function decline and sudden cardiac death within the first year of life, is anticipated to contribute greatly to the elucidation of inherited arrhythmia’s pathogenesis and the assessment of drug efficacy.
Journal: PNAS
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