“This paper shows that circadian clocks in peripheral tissues can persist for at least 20 cycles in culture and shows that the master pacemaker in the suprachiasmatic nucleus (SCN) is not required for these peripheral rhythms.”

This paper reports an improved bioluminescence reporter mouse using gene-targeting methods to produce a PERIOD2::LUCIFERASE fusion protein. The PER2::LUC fusion protein functions normally and allows one to measure circadian rhythms of bioluminescence in tissues and cells in real time in vitro. This paper shows that circadian clocks in peripheral tissues can persist for at least 20 cycles in culture and shows that the master pacemaker in the suprachiasmatic nucleus (SCN) is not required for these peripheral rhythms. Taken together, these results refute the previous dogma that only the SCN clock is persistent, that peripheral clocks have damped rhythms, and that the SCN drives persistent rhythms in peripheral tissues. Rather, these results suggest that the SCN acts as a synchronizer of circadian rhythms generated by peripheral tissues.

Yes, a new and improved bioluminescence reporter mouse using gene-targeting methods ("knock in") to produce a PER2::LUC fusion protein. The PER2::LUC fusion protein can reflect both the transcriptional and post-transcriptional regulation of the PER2 protein (which are both important levels of circadian control). In addition, the use of knock-in technology allows the preservation of gene regulatory elements in the context of the native locus. The PER2::LUC knock-in mice are being widely distributed and are being used by many laboratories worldwide.

These experiments allow us to monitor circadian rhythms in virtually every tissue in the animal (mouse). This has revealed that almost every tissue and organ in the body contains intrinsic circadian clocks. These body clocks are autonomous, but they are normally synchronized by a master clock located in the brain (in a structure called the "SCN").

My laboratory is interested in the molecular mechanism of the circadian clock. We have contributed to the discovery of a number of the "core circadian clock genes" in mammals. These circadian genes were found to be expressed in virtually all tissues in the brain and body. The PER2 gene in particular has a very high amplitude circadian rhythm in most tissues and this makes the PER2 protein an ideal marker for circadian rhythms. The fusion of luciferase to the PER2 protein creates a very sensitive circadian bioluminescence reporter.