Z-Tag for Measuring Cardiac Contractility and Cardiac Rhythmicity

描述(由申请人提供)：关于正在开发的药物的一个主要问题是心脏毒性。通常，开发中的药物会导致心脏收缩能力、心脏跳动的力量和心律失常的变化，从而导致毒副作用。这一第一阶段建议的目的是开发斑马鱼检测方法，用于测量药物引起的心肌收缩能力和心律失常的变化。这些检测将使用转基因斑马鱼品系来开发，该转基因斑马鱼品系专门在心脏表达一种绿色荧光报告蛋白。将开发评估斑马鱼收缩和节律性的方法。已知会导致人类心脏收缩能力和节律性变化的药物将使用这些斑马鱼进行测试，以验证测试结果。这些检测方法的开发将允许对正在开发的心脏毒性药物进行高通量的体内测试。

DESCRIPTION (provided by applicant): A major concern regarding drugs in development is cardiac toxicity. Commonly, drugs in development can cause changes to cardiac contractility, the force with which the heart beats, and cardiac rhythmicity, resulting in toxic side effects. The purpose of this Phase 1 proposal is to develop zebrafish assays for measuring drug-induced changes in cardiac contractility and cardiac rhythmicity. These assays will be developed using a transgenic zebrafish line expressing a green fluorescent reporter protein specifically in the heart. Methods of assessing contractility and rhythmicity in zebrafish will be developed. Drugs that are known to cause changes to cardiac contractility and rhythmicity in humans will be tested using these zebrafish in order to validate the assay. Development of these assays will allow high-throughput, in vivo testing of drugs in development for cardiac toxicity.