Dudley Carol A, Erbel-Sieler Claudia, Estill Sandi Jo, Reick Martin, Franken Paul, Pitts SiNae, McKnight Steven L
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.
Science. 2003 Jul 18;301(5631):379-83. doi: 10.1126/science.1082795. Epub 2003 Jul 3.
Animal behavior is synchronized to the 24-hour light:dark (LD) cycle by regulatory programs that produce circadian fluctuations in gene expression throughout the body. In mammals, the transcription factor CLOCK controls circadian oscillation in the suprachiasmatic nucleus of the brain; its paralog, neuronal PAS domain protein 2 (NPAS2), performs a similar function in other forebrain sites. To investigate the role of NPAS2 in behavioral manifestations of circadian rhythm, we studied locomotor activity, sleep patterns, and adaptability to both light- and restricted food-driven entrainment in NPAS2-deficient mice. Our results indicate that NPAS2 plays a substantive role in maintaining circadian behaviors in normal LD and feeding conditions and that NPAS2 is critical for adaptability to food restriction.
动物行为通过调控程序与24小时昼夜(光:暗,LD)循环同步,这些调控程序会在全身产生基因表达的昼夜波动。在哺乳动物中,转录因子CLOCK控制着大脑视交叉上核中的昼夜节律振荡;其旁系同源物神经元PAS结构域蛋白2(NPAS2)在其他前脑部位发挥类似功能。为了研究NPAS2在昼夜节律行为表现中的作用,我们研究了NPAS2基因敲除小鼠的运动活动、睡眠模式以及对光驱动和食物限制驱动的昼夜节律调整的适应性。我们的结果表明,NPAS2在正常LD和进食条件下维持昼夜节律行为中发挥着重要作用,并且NPAS2对于适应食物限制至关重要。