Genetic Defects of the Mammalian Circadian clock and Pre

描述（由申请人提供）：大量信息表明，从细菌到人类的活生物体的生理和行为受昼夜节律控制，昼夜节律由内源性振荡器驱动，以响应日常环境线索。第一个基因编码的分子球员的昼夜节律钟，周期（每）是在果蝇中确定的。我的实验室在鉴定两种哺乳动物时期同源物mPerl和mPer2方面发挥了重要作用。我们最近提供的遗传证据表明，mPerl和mPer2确实是控制昼夜节律的关键角色。mPer2基因的功能缺失突变导致昼夜节律控制的丧失。mPerl基因的缺失影响了生物钟周期的精确控制，但突变动物保留了昼夜节律。然而，mPerl和mPer2的丢失导致完全缺乏生物钟活动。对这些生物钟缺陷动物的一个有趣的观察，特别是那些有mPer2突变的动物，它们显然过早衰老。在这个建议中，我们想测试的假设，昼夜节律钟是一个明显的时钟参与衰老。具体来说，我们想了解线粒体稳态的生物钟控制。

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.