Circadian timekeeping in hamster mutants

项目摘要 反常的光暴露会扰乱人类的日常节律，并与许多疾病有关。这是一场严肃的 公众健康问题，因为夜间的灯光影响高达80%的美国人。此外，基因中的多态 昼夜节律基因改变了睡眠和对光的反应，从而产生了很高的个人和社会负担。 尽管在这一领域取得了许多进展，但在理解分子时钟如何变化方面仍存在重大差距 功能转化为表型和病理。一个障碍是普遍使用缺乏 全身性提示存在于人类和其他哺乳动物中(例如，褪黑素)。叙利亚仓鼠是一种褪黑素- 能干的啮齿动物，对光有令人印象深刻的昼夜和光周期反应。拥有 在仓鼠模型中开发了第一个昼夜节律记者，在这里我们将在 在这个信息丰富的物种中，中央和系统级别的。此外，我们将利用具有良好特征的突变 存在于仓鼠体内，影响生物钟功能、光携带和生理学。这项工作将 为使用该动物模型获得更全面的昼夜节律和 影响健康的光周期过程。

PROJECT ABSTRACT Aberrant light exposure disrupts daily rhythms in humans and is linked to many diseases. This is a serious public health concern because light at night impacts up to 80% of Americans. Further, polymorphisms in circadian genes alter sleep and responses to light, which produces high personal and societal burdens. Despite many gains in the field, a major gap remains in understanding how changes in molecular clock function translate into phenotype and pathology. One obstacle is the common use of mouse models that lack systemic cues present in humans and other mammals (e.g., melatonin). The Syrian hamster is a melatonin- competent rodent with an impressive repertoire of circadian and photoperiodic responses to light. Having developed the first circadian reporter in a hamster model, here we will investigate circadian timekeeping at the central and systems-level in this informative species. Further, we will leverage well-characterized mutations present in the hamster that affect circadian clock function, photoentrainment, and physiology. This work will lay the essential foundations to use this animal model to gain a more holistic understanding circadian and photoperiodic processes that impact health.