NPAS2:在哺乳动物前脑中运行时钟的类似物
M Reick1, J A Garcia, C Dudley
1Department of Biochemistry, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|July 7, 2001
概括
神经PAS域蛋白2 (NPAS2) 在哺乳动物前脑分子钟中起作用. NPAS2,以及BMAL1,通过控制关键时钟基因表达来调节昼夜节律.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 时间生物学 时间生物学
背景情况:
- 神经PAS域蛋白2 (NPAS2) 是一种在哺乳动物前脑中发现的转录因子.
- NPAS2与CLOCK具有序列相似性,这是一个已知的昼夜节律调节器.
- 在大脑的分子钟中NPAS2的确切作用尚未完全阐明.
研究的目的:
- 为了研究NPAS2在哺乳动物前脑中的生物功能.
- 为了识别由NPAS2:BMAL1异构体调节的基因.
- 确定NPAS2对大脑中昼夜节律的贡献.
主要方法:
- 在神经母细胞瘤细胞系中条件诱导NPAS2:BMAL1异构体.
- 使用表示差异分析,DNA微阵列和北方斑点识别目标基因.
- 在野生类型和NPAS2缺陷小鼠中分析Per1,Per2和BMAL1mRNA表达.使用in situ杂交.
主要成果:
- 对NPAS2和BMAL1的同诱导激活了Per1,Per2和Cry1的转录,这是一个关键的昼夜组件.
- NPAS2:BMAL1异构体抑制了BMAL1基因的转录.
- NPAS2缺陷扰乱了小鼠前皮层中Per2 mRNA的昼夜振荡.
结论:
- 在哺乳动物前脑中,NPAS2在调节昼夜基因表达方面发挥着至关重要的作用.
- NPAS2 作为前脑分子钟的组成部分.
- 这些发现有助于理解昼夜节律的神经生物学基础.
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