Loss of Bmal1 in the SCN/brain of adult mice

成年小鼠 SCN/大脑中 Bmal1 缺失

• 批准号: 7491503
• 负责人: MARTINA PEJCHAL
• 金额: $ 2.91万
• 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/7491503
• 关键词: Ablation; Address; Adult; Age; Animals; Area; Biological Rhythm; Brain; Circadian Rhythms; Clock protein; Conceptions; Condition; Darkness; Disruption; Doxycycline; Electronic Mail; Feedback; Future; Gene Expression; Genes; Genetic; Health; Human; Hypothalamic structure; Impairment; Jet Lag Syndrome; Knock-out; Laboratories; Lead; Lesion; Liver; Luciferases; Mammals; Methamphetamine; Molecular; Monitor; Motor Activity; Mus; Organism; Peripheral; Phenotype; Regulation; Reporter; Research Proposals; Rest; Role; Running; Specificity; System; Technology; Testing; Tetracycline; Tetracyclines; Time; Tissues; Trans-Activators; Transact; Transgenes; Transgenic Mice; Transgenic Organisms; promoter; reproductive; shift work; suprachiasmatic nucleus

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）： 肌次核（SCN）是哺乳动物中许多生物节奏的主要调节剂，并将其余的生物体同步到光黑暗循环。这种同步的破坏，就像在轮班工作，喷气滞后和老年中发生的那样，会对人类健康产生严重影响。因此，重要的研究领域是SCN，其他大脑区域和身体组织之间相对于各种昼夜节律的相互作用。通过在SCN和某些大脑区域中对核心时钟基因BMAL1进行四环素调节的敲除，该研究建议将解决成年小鼠中这些区域中BMAL1的损失是否也会废除运动活动的昼夜节律。作为MPER2 :: LUC振荡的同步。这种条件的BMAL1敲除也可以用于对肝脏夹带中心调节的未来研究，以及这些大脑区域中的BMAL1是否参与甲基苯丙胺引起的预期运动活性。最终，BMAL1参与了非circadian异常，例如关节炎和生殖障碍，此处提出的BMAL1敲除将有助于将来的研究，以区分这些表型中中央和周围BMAL1的作用。