Z-Tag for Measuring Cardiac Contractility and Cardiac Rhythmicity

描述（由申请人提供）：关于开发中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力（心脏跳动的力量）和心律的变化，从而导致毒副作用。本1期提案的目的是开发用于测量药物诱导的心肌收缩力和心律变化的斑马鱼测定。将使用在心脏中特异性表达绿色荧光报告蛋白的转基因斑马鱼系开发这些测定。将开发评估斑马鱼收缩性和节律性的方法。已知会引起人类心脏收缩力和节律性变化的药物将使用这些斑马鱼进行测试，以验证该测定法。这些检测方法的开发将允许对开发中的药物进行心脏毒性的高通量体内检测。

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.