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奏，并与许多疾病有关。这是一个严重 公共卫生问题，因为夜间光线影响高达80%的美国人。此外，多态性在 昼夜节律基因会改变睡眠和对光的反应，这会给个人和社会带来沉重的负担。 尽管在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。一个障碍是普遍使用的小鼠模型， 存在于人类和其它哺乳动物中的系统性线索（例如，褪黑激素）。叙利亚仓鼠是褪黑激素- 有能力的啮齿动物，对光线有着令人印象深刻的昼夜节律和光周期反应。具有 在仓鼠模型中开发了第一个昼夜节律报告者，在这里，我们将研究在 在这个信息丰富的物种中的中心和系统水平。此外，我们将利用特征良好的突变 存在于仓鼠中，影响生物钟功能、光诱导和生理学。这项工作将 为使用这种动物模型来更全面地了解昼夜节律奠定了必要的基础， 影响健康的光周期过程。