Clarification of molecular mechanism of Jet Lag

我们发现，PER1基因敲除(PER1-/-)小鼠是一种可以较早重新进入实验新时区的时差模型动物。在光照过程中，核心时钟蛋白PER2蛋白、主钟节律蛋白(SCN)的运动幅度较大，而PER2基因的表达没有发生变化。PER1对PER2的这种蛋白质水平调节是时差的一个原因。此外，我们还发现PER1-/-小鼠几乎不能适应夜间生活的实验长光周期(骨骼光周期，低光强)。这一结果表明，PER1基因有助于祖先哺乳动物的夜间生存。接下来，我们在PER1-/-小鼠的SCN中寻找了PER2蛋白和mRNA解离过程中基因的转录图谱。为了准确采集SCN样本，我们建立了PER1-/-小鼠近交系(回交10次)。我们通过PCR消减技术在PER1-/-小鼠中发现了大量时差任务诱导的基因，并通过原位杂交证实了这些基因表达的变化。

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.