一个分子机制调节节律输出从suprachiasmatic昼夜时钟的节奏
X Jin1, L P Shearman, D R Weaver
1Pediatric Service, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Cell
|February 16, 1999
概括
核心分子时钟直接控制大脑中阿尔金血压素基因的日常节奏. 破坏时钟基因取消了血管压素节奏,影响了水平.
科学领域:
- 神经科学是一个神经科学.
- 时间生物学 时间生物学
- 分子生物学分子生物学
背景情况:
- 小鼠的上神核 (SCN) 产生昼夜节律.
- 一个涉及CLOCK,BMAL1和mPer基因的核心转录反循环调节SCN时钟.
研究的目的:
- 为了研究SCN中阿尔金因血管压素 (AVP) 基因的转录调节,一个时钟控制的输出,在SCN中.
- 阐明核心时钟组件在调节AVP基因表达节奏中的作用.
主要方法:
- 在野生型和时钟/时钟突变小鼠中分析基因表达节奏.
- 路西法酶记者基因测试以评估CLOCK-BMAL1异构体的转录激活.
主要成果:
- 在Clock/Clock小鼠中,mPer基因的RNA节奏显著减弱.
- 在Clock/Clock小鼠中,血管压素RNA节奏被废除,导致水平降低.
- 时钟-BMAL1异构体通过E盒增强剂激活血管压素转录,被mPER和mTIM抑制.
结论:
- 核心分子时钟机械直接调节时钟控制的输出节奏,例如氨酸.
- 时钟-BMAL1异构体是血管压素节律的关键正调节体.
- 在这种转录反循环中,mPER和mTIM蛋白质充当负调节剂.
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