Genetic Defects of the Mammalian Circadian clock and Pre

哺乳动物昼夜节律钟的遗传缺陷和预

• 批准号: 7276648
• 负责人: CHENG CHI LEE
• 金额: $ 31.62万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276648
• 关键词: Affect; Age; Aging; Animals; Bacteria; Behavior; Biological Pacemakers; Circadian Rhythms; Cues; DNA Damage; DNA Microarray Chip; DNA Microarray format; Daily; Drosophila genus; Genes; Genetic; Genotoxic Stress; Goals; Homeostasis; Homologous Gene; Human; Ionizing radiation; Laboratories; Life; Microarray Analysis; Mitochondria; Molecular; Mutation; Organism; Oxidation-Reduction; Pathogenesis; Pathway interactions; Periodicity; Physiology; Premature aging syndrome; Proteins; Rate; Reactive Oxygen Species; Regulation; Role; Stress; Testing; aged; circadian pacemaker; interest; loss of function mutation; mutant; response

DESCRIPTION (provided by applicant): A large body of information has indicated that the physiology and behavior of living organisms from bacteria to humans are controlled by circadian rhythms driven by endogenous oscillators in response to daily environmental cues. The first gene encoding a molecular player of the circadian clock, period (per) was identified in Drosophila. My laboratory was instrumental in the identification of two mammalian period homologue, mPerl and mPer2. We have recently provided genetic evidences that mPerl and mPer2 are indeed key players in the control of the circadian. Loss of function mutation of mPer2 gene results in the loss in control of circadian rhythmicity. The loss of mPerl gene affects the precision control of the clock period but the mutant animals retained circadian rhythmicity. However, a loss of both mPerl and mPer2 results in a complete absence of circadian clock activity. An interesting observation of these clock defective animals, especially those with mPer2 mutation is that they apparently age prematurely. In this proposal, we would like to test the hypothesis that the circadian clock is an overt clock involved in aging. Specifically we would like to understand circadian clock control of mitochondria homeostasis.

描述（由申请人提供）：大量信息表明，从细菌到人类的生物体的生理和行为由内源性振荡器驱动的昼夜节律控制，这是对日常环境提示的响应。编码昼夜节律时钟的第一个基因，在果蝇中确定了周期（per）。我的实验室有助于鉴定两个哺乳动物时期同源物，MPERL和MPER2。我们最近提供了遗传证据，即MPERL和MPER2确实是昼夜节律控制的关键参与者。 MPER2基因功能突变的丧失导致控制昼夜节律的丧失。 MPER基因的丧失会影响时钟周期的精确控制，但突变动物保留了昼夜节律。但是，MPERL和MPER2的损失均导致昼夜节律活动完全没有。对这些时钟有缺陷的动物，尤其是MPER2突变的动物的一个有趣的观察是，它们显然过早地年龄。在此提案中，我们想检验以下假设：昼夜节律是参与衰老的公开时钟。具体来说，我们想了解线粒体稳态的昼夜节律控制。

项目成果

p53 regulates Period2 expression and the circadian clock.

• DOI: 10.1038/ncomms3444
• 发表时间: 2013
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Miki, Takao;Matsumoto, Tomoko;Zhao, Zhaoyang;Lee, Cheng Chi
• 通讯作者: Lee, Cheng Chi