Genetics of Sleep in Zebrafish

描述（由研究者提供）：拟作项目的长期目标是确定调节脊椎动物睡眠和觉醒的基因。我们将使用斑马鱼作为这类研究的遗传系统，因为鱼具有基本的大脑结构和调节人类睡眠的肽。我们开发了高通量的方法来测量斑马鱼的睡眠和清醒状态，发现下丘脑分泌素/食欲素信号的作用在斑马鱼和哺乳动物之间是保守的。我们将筛选1000种不同的斑马鱼系，这些斑马鱼系在成年大脑中表达的基因中含有破坏性插入，并且有可能成为药物靶点。突变体将通过运动活动和觉醒阈值来筛选睡眠和觉醒缺陷。这些研究将确定参与睡眠生物学的基因，并为大量生物医学相关基因提供功能数据。

DESCRIPTION (provided by investigator): The long-range goal of the proposed project is to identify genes that regulate sleep and wakefulness in vertebrates. We will use zebrafish as a genetic system for such studies, because fish have the basic brain structures and peptides that regulate sleep in humans. We have developed high-throughput assays to measure sleep and wakefulness in zebrafish and found that the role of Hypocretin/Orexin signaling is conserved between zebrafish and mammals. We will screen 1,000 different zebrafish lines harboring disruptive insertions in genes that are expressed in the adult brain and have the potential to be drug targets. Mutants will be screened for defects in sleep and wakefulness using locomotor activity and arousal threshold. These studies will identify genes involved in sleep biology and provide functional data for a large number of biomedically relevant genes. PUBLIC HEALTH RELEVANCE: As many as 10% of Americans suffer chronic sleep disturbances, but the genetic mechanisms that control sleep and wake states remain largely unknown. The discovery of genes that regulate sleep in zebrafish will help to uncover the molecular underpinnings of sleep and inform strategies for the treatment of sleep disorders.