Circadian timekeeping in hamster mutants

仓鼠突变体的昼夜节律

• 批准号: 10790160
• 负责人: ERIC L BITTMAN
• 金额: $ 42.47万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10790160
• 关键词: Affect; American; Animal Model; Behavior; Behavioral; Biology; Brain; Cardiovascular Diseases; Cell physiology; Circadian Dysregulation; Circadian Rhythms; Crying; Cues; Darkness; Disease; Feedback; Foundations; Gene Expression; Genes; Genetic Polymorphism; Genetic Transcription; Hamsters; Health; Human; Immunologic Deficiency Syndromes; Impaired cognition; Jet Lag Syndrome; Light; Link; Mammals; Melatonin; Mesocricetus auratus; Modeling; Molecular; Mus; Mutation; Nerve Degeneration; Nervous System Physiology; Obesity; Optics; Pathologic; Pathology; Phenotype; Physiological; Physiology; Process; Public Health; Rattus; Reporter; Reporter Genes; Risk; Rodent; Sleep; System; Testing; Tissues; Translating; Work; cancer risk; circadian; circadian pacemaker; day length; human disease; insight; interest; molecular clock; mouse model; mutant; novel; photoperiodicity; reproductive; response; screening; suprachiasmatic nucleus; tau Proteins

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.

项目摘要 异常的光照会扰乱人类的日常节律，并与许多疾病有关。这是一个严重的 公共健康问题，因为夜间光线影响多达 80% 的美国人。此外，多态性 昼夜节律基因改变睡眠和对光的反应，从而产生沉重的个人和社会负担。 尽管该领域取得了许多进展，但在理解分子钟如何变化方面仍然存在重大差距 功能转化为表型和病理学。一个障碍是普遍使用的小鼠模型缺乏 人类和其他哺乳动物中存在的系统线索（例如褪黑激素）。叙利亚仓鼠是一种褪黑素 具有令人印象深刻的昼夜节律和光周期对光反应的啮齿动物。拥有 在仓鼠模型中开发了第一个昼夜节律报告器，在这里我们将研究昼夜节律计时 在这个信息丰富的物种中处于中央和系统级别。此外，我们将利用特征明确的突变 存在于仓鼠中，影响生物钟功能、光诱导和生理机能。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。