Mouse models of arrhythmogenic cardiovascular disease: challenges and opportunities

• ECG and action potential waveforms are markedly different in humans and mice.
• Mouse models of Scn5a channelopathies recapitulate many aspects of human disease.
• Distinct repolarization mechanisms limit mouse models of human Kv channelopathies.
• Mouse models of Ca2+ dependent arrhythmias provide novel cellular insights.
• Electrical remodeling and reprogramming mechanisms are increasingly probed in mice.

Arrhythmogenic cardiovascular disease is associated with significant morbidity and mortality and, in spite of therapeutic advances, remains an enormous public health burden. The scope of this problem motivates efforts to delineate the molecular, cellular and systemic mechanisms underlying increased arrhythmia risk in inherited and acquired cardiac and systemic disease. The mouse is used increasingly in these efforts owing to the ease with which genetic strategies can be exploited and mechanisms can be probed. The question then arises whether the mouse has proven to be a useful model system to delineate arrhythmogenic cardiovascular disease mechanisms. Rather than trying to provide a definite answer, the goal here is to consider the issues that arise when using mouse models and to highlight the opportunities.