A Screen for Identifying Insomnia Genes

项目摘要 进化医学利用自然产生的表型差异的力量，通过 适应研究潜在疾病的遗传机制，包括神经障碍。这个 墨西哥穴居鱼与其祖先的同类表层鱼相比，表现出显著的睡眠不足 为识别调节睡眠的遗传因素提供了一个独特而强大的模型。建议数 实验将在墨西哥穴居鱼中实施基因技术，以确定天然的新调控因子 在穴居鱼中出现类似失眠的表型。这项提议还将适用于一种新开发的 神经解剖脑图谱和全脑钙成像确定新的睡眠基因如何影响 大脑的结构和功能。这些实验将对睡眠的机制基础提供重要的见解 调节并识别有助于睡眠调节的自然发生的遗传变异。此外， 这些研究中建立的遗传工具和方法学将提供可应用的宝贵资源 解决超出本提案范围的问题，包括眼睛退化、肥胖、 在这个系统中通常被研究的吞噬过多和攻击性。

Project Summary Evolutionary medicine leverages the power of naturally occurring phenotypic differences derived through adaptation to investigate genetic mechanisms underlying diseases, including neurological disorders. The Mexican cavefish exhibits a dramatic evolution of sleep loss compared to ancestral surface fish of the same species, providing a unique and powerful model to identify genetic factors regulating sleep. The proposed experiments will implement genetic technology in Mexican cavefish to identify novel regulators of naturally occurring insomnia-like phenotypes in cavefish. This proposal will also apply a newly developed neuroanatomical brain atlas and whole-brain calcium imaging to determine how novel sleep genes impact brain structure and function. These experiments will provide critical insight into the mechanistic basis of sleep regulation and identify naturally occurring genetic variants that contribute to sleep regulation. Further, the genetic tools and methodology established in these studies will provide valuable resources that can be applied to address questions beyond the scope in this proposal, including diseases such as eye-degeneration, obesity, hyperphagia and aggression that are commonly studied in this system.