Clarification of molecular mechanism of Jet Lag

我们发现Per 1基因敲除（Per 1-/-）小鼠是一种时差模型动物，可以更早地重新进入实验新时区。在照明任务期间，PER 2蛋白，核心时钟蛋白，主时钟（SCN）中的节奏大幅移动，而不改变Per 2 mRNA的增加。PER 1对PER 2的这种蛋白质水平调节是时差综合征的原因。另外，我们发现Per 1-/-小鼠几乎不能进行实验性的长光周期夜间生活（具有骨骼光周期，低光强）。本研究进一步探讨了Per 1-/-小鼠SCN中Per 2蛋白与mRNA分离过程中基因的转录谱。为了精确地对SCN进行取样，我们建立了Per 1-/-小鼠的近交系（回交10次）。我们利用PCR消减技术在Per 1-/-小鼠中发现了大量时差反应诱导的基因，并通过原位杂交证实了这些基因表达的移动。

We found that Per1 knockout (Per1-/-) mouse is a jet lag model animal which can re-entrain to experimental new time zone earlier. During the lighting task PER2 protein, core clock protein, rhythm in the master clock (SCN) moves largely without changing the Per2 mRNA increase. This protein level regulation of PER2 by PER1 is a cause of Jet Lag. In addition, we found Per1-/- mouse can hardly entrain to experimental long photoperiod for nocturnal life (with skeleton photoperiod, low light intensity). This result suggests that Per1 gene aided nocturnal survival life of ancestral mammals.We next searched the transcriptional profiles of genes in the SCN during the dissociation between Per2 protein and mRNA in Per1-/- mouse. To sample SCN precisely, we established inbred line of Per1-/- mouse (backcrossed for ten times). We found largely induced genes by jet lag task in Per1-/- mouse by PCR subtraction technique and confirmed these movements of gene expressions by in situ hybridization.