Tissue-specific interaction of Per1/2 and Dec2 in the regulation of fibroblast circadian rhythms.

In mammals, the molecular circadian clockwork is comprised of interlocked transcriptional-translational feedback loops (TTLs). Three Period (Per1-3) and 2 Dec (Dec1/2) genes interact in regulating the activity of the transcriptional activators CLOCK/NPAS2 and BMAL1. While deletion of Per1 and Per2 in mice results in behavioral arrhythmicity, Dec deletion has less dramatic effects on activity rhythms, affecting primarily phase of entrainment and free-running period.

Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork.

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork.

Genetic interaction of Per1 and Dec1/2 in the regulation of circadian locomotor activity.

In mammals, 24-h rhythms are controlled by a hierarchical system of endogenous clocks, with a circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus that synchronizes peripheral oscillators throughout the body. The molecular clock machinery is regulated by interlocked transcriptional translational feedback loops (TTLs). The core TTL includes the transcriptional modulators PER (1-3) and CRY (1/2) that feed back on their own expression by interaction with CLOCK/BMAL1.

Advanced light-entrained activity onsets and restored free-running suprachiasmatic nucleus circadian rhythms in per2/dec mutant mice.

Many behavioral and physiological processes display diurnal (24-h) rhythms controlled by an internal timekeeping system?the circadian clock. In mammals, a circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronizes peripheral oscillators found in most other tissues with the external light-dark (LD) cycle. At the molecular level, circadian clocks are regulated by transcriptional translational feedback loops (TTLs) involving a set of clock genes.