Loss of Bmal1 in the SCN/brain of adult mice

成年小鼠 SCN/大脑中 Bmal1 缺失

• 批准号: 7156688
• 负责人: MARTINA PEJCHAL
• 金额: $ 3.07万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156688
• 关键词: brain; circadian rhythms; genes; genetics; proteins; tetracyclines; tissues

DESCRIPTION (provided by applicant): The Suprachiasmatic Nucleus (SCN) is the main regulator of many biological rhythms in mammals and synchronizes the rest of the organism to the light-dark cycle. Disruption of this synchronization, as happens during shift work, jet lag, and old age, results in a serious impact on human health. Therefore an important area of study is the interaction between the SCN, other brain areas, and body tissues with respect to various circadian rhythms. By making a tetracycline-regulated knock-out of a core clock gene, Bmal1, in the SCN and some brain areas, this research proposal will address whether loss of Bmal1 in these areas in an adult mouse will abolish circadian rhythms of locomotor activity as well as synchrony of mPER2::LUC oscillations in peripheral tissues. This conditional Bmal1 knock-out can also be used for future studies of central regulation of liver entrainment as well as whether Bmal1 in these brain areas is involved in methamphetamine-induced anticipatory locomotor activity. Finally Bmal1 is involved in non-circadian abnormalities such as arthropathy and reproductive impairment, and the Bmal1 knock-out proposed here will be helpful for future studies distinguishing the roles of central and peripheral Bmal1 in these phenotypes.

描述（由申请人提供）： 视交叉上核 (SCN) 是哺乳动物许多生物节律的主要调节器，并使生物体的其余部分与光暗周期同步。这种同步性的破坏，如轮班工作、时差反应和年老时发生的情况，会对人类健康造成严重影响。因此，一个重要的研究领域是视交叉上核、其他大脑区域和身体组织在各种昼夜节律方面的相互作用。通过四环素调节敲除 SCN 和一些大脑区域中的核心时钟基因 Bmal1，这项研究计划将解决成年小鼠这些区域中 Bmal1 的缺失是否也会废除运动活动的昼夜节律。作为外周组织中 mPER2::LUC 振荡的同步。这种条件性 Bmal1 敲除还可用于未来研究肝脏夹带的中枢调节以及这些大脑区域中的 Bmal1 是否参与甲基苯丙胺诱导的预期运动活动。最后，Bmal1 涉及非昼夜节律异常，例如关节病和生殖障碍，本文提出的 Bmal1 敲除将有助于未来研究区分中枢和外周 Bmal1 在这些表型中的作用。