Segregation of expression of mPeriod gene homologs in neurons and glia: possible divergent roles of mPeriod1 and mPeriod2 in the brain
Segregation of expression of mPeriod gene homologs in neurons and glia: possible divergent roles of mPeriod1 and mPeriod2 in the brain
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DOI：
10.1093/hmg/ddp252
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发表时间：
2009-08-15
影响因子：
3.5
通讯作者：
Obrietan, Karl
中科院分区：
文献类型：
--
作者：
Cheng, Hai-Ying M.;Alvarez-Saavedra, Matias;Obrietan, Karl
哺乳动物下丘脑的视交叉上核(SCN)起着生物钟的作用，协调不同细胞群和器官系统的时间。时钟时间的失调与一系列人类疾病有关，包括肥胖、心血管疾病和一系列神经疾病。周期基因表达的异常调节与细胞分裂异常和人类癌症有关，而常染色体显性遗传病家族性晚期睡眠相综合征被定位于关键时钟基因hPERIOD2内的一个错义突变。要开始剖析内在的分子计时过程，一个必不可少的工具是时钟基因报告。在这里，我们对两个新的转基因小鼠时钟报告器mPerod1-Venus和mPerod2-DsRED进行了功能鉴定。Venus和DsRED是荧光蛋白，可用于实时监测单个细胞的转录。对SCN的成像显示了Venus和DsRED表达的振荡和光诱导。在不同的SCN细胞群体中观察到有节律性的Venus和DsRED表达，这表明存在离散的细胞SCN时钟。除SCN外，mPerod1-Venus在神经元和非神经元群体中广泛表达。相反，mPerod2-DsRED在齿状回的神经胶质细胞群和前体细胞中表达；在神经元中表达有限。这两位记者的这种不同的表达模式表明，中枢神经系统拥有机械上不同的神经元和非神经元细胞时钟亚群。这些新颖的小鼠模型将有助于我们理解时钟计时及其在人类疾病中的作用。
The suprachiasmatic nuclei (SCN) of the mammalian hypothalamus function as the master circadian clock, coordinating the timing of diverse cell populations and organ systems. Dysregulation of clock timing is linked to a broad range of human conditions, including obesity, cardiovascular disease and a wide spectrum of neurological disorders. Aberrant regulation of expression of the PERIOD genes has been associated with improper cell division and human cancers, while the autosomal dominant disorder familial advanced sleep phase syndrome has been mapped to a single missense mutation within the critical clock gene hPERIOD2. An essential tool to begin to dissect the inherent molecular timing process is the clock gene reporter. Here, we functionally characterize two new mouse transgenic clock reporters, mPeriod1-Venus and mPeriod2-DsRED. Venus and DsRED are fluorescent proteins that can be used to monitor transcription in individual cells in real-time. Imaging of the SCN revealed oscillations, as well as light inducibility, in Venus and DsRED expression. Rhythmic Venus and DsRED expression was observed in distinct SCN cell populations, suggesting the existence of discrete cellular SCN clocks. Outside of the SCN, mPeriod1-Venus expression was broadly expressed in neuronal and non-neuronal populations. Conversely, mPeriod2-DsRED was expressed in glial populations and progenitor cells of the dentate gyrus; limited expression was detected in neurons. This distinct expression pattern of the two reporters reveals that the central nervous system possesses mechanistically distinct subpopulations of neuronal and non-neuronal cellular clocks. These novel mouse models will facilitate our understanding of clock timing and its role in human diseases.