Genetics of Sleep in Zebrafish

多达10%的美国人患有慢性睡眠障碍，但控制睡眠和觉醒状态的遗传机制在很大程度上仍然未知。这项研究的长期目标是确定调节睡眠、觉醒和觉醒的分泌蛋白。斑马鱼将被用作模型系统，因为它显示清晰，可测量的睡眠和觉醒行为，并且是唯一可行的脊椎动物系统。该筛选将涉及数百个稳定转基因斑马鱼系的产生，这些斑马鱼系在诱导型启动子下表达分泌蛋白。该文库将通过斑马鱼储备中心提供，并筛选幼虫睡眠和觉醒的调节剂。此外，还将测试对机械、化学、热和视觉线索的反应。候选品系将在发育和行为缺陷的二次筛选中进一步分析。分离的肽将成为剖析睡眠的分子和神经回路的基础。该筛选还将提供可能影响人类睡眠障碍的候选途径，并且可以通过药物调节来治疗睡眠障碍。

DESCRIPTION (provided by applicant): As many as 10% of Americans suffer chronic sleep disturbances, but the genetic mechanisms that control sleep and wake states remain largely unknown. The long-range goal of the proposed studies is to identify secreted proteins that modulate sleep, wakefulness and arousal. Zebrafish will be used as a model system because it displays clear, measurable sleep and wake behaviors and is the only vertebrate system in which such a screen is feasible. The screen will involve the generation of several hundred stably transgenic zebrafish lines that express secreted proteins under an inducible promoter. The library will be made available through the zebrafish stock center and screened for modulators of larval sleep and wakefulness. In addition, the response to mechanical, chemical, thermal and visual cues will be tested. Candidate lines will be further analyzed in secondary screens for developmental and behavioral defects. The isolated peptides will form the foundation to dissect the molecular and neural circuits of sleep. The screen will also provide candidate pathways that might be affected in human sleep disorders and that could be modulated by drugs to treat sleep disorders.