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PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues

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TLDR
It is demonstrated that peripheral tissues express self-sustained, rather than damped, circadian oscillations and the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level is suggested.
Abstract
Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), and current dogma holds that the SCN is required for the expression of circadian rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a real-time reporter of circadian dynamics in mice, we report that, contrary to previous work, peripheral tissues are capable of self-sustained circadian oscillations for >20 cycles in isolation. In addition, peripheral organs expressed tissue-specific differences in circadian period and phase. Surprisingly, lesions of the SCN in mPer2Luciferase knockin mice did not abolish circadian rhythms in peripheral tissues, but instead caused phase desynchrony among the tissues of individual animals and from animal to animal. These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level.

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Citations
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Journal ArticleDOI

Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice

TL;DR: Estimation of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice, suggesting that the circadian clock gene network plays an important role in mammalian energy balance.
Journal ArticleDOI

The mammalian circadian timing system: organization and coordination of central and peripheral clocks.

TL;DR: This work discusses knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system and some of the SCN output pathways serve as input pathways for peripheral tissues.
Journal ArticleDOI

Central and Peripheral Circadian Clocks in Mammals

TL;DR: An emerging view for the adaptive significance of circadian clocks is their fundamental role in orchestrating metabolism.
Journal ArticleDOI

Molecular components of the mammalian circadian clock

TL;DR: The general mechanisms of the circadian clockwork are reviewed, recent findings that elucidate tissue-specific expression patterns of the clock genes are described and the importance of circadian regulation in peripheral tissues for an organism's overall well-being is addressed.
Journal ArticleDOI

The Genetics of Mammalian Circadian Order and Disorder: Implications for Physiology and Disease

TL;DR: Together, these studies set the scene for applying the knowledge of circadian biology to the understanding and treatment of a range of human diseases, including cancer and metabolic and behavioural disorders.
References
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Journal ArticleDOI

Coordination of circadian timing in mammals

TL;DR: Circadian rhythms are generated by one of the most ubiquitous and well-studied timing systems and are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.
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Coordinated transcription of key pathways in the mouse by the circadian clock.

TL;DR: Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components, and major processes regulated by the SCN and liver were found to be under circadian regulation.
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Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus

TL;DR: It is shown that temporal feeding restriction under light-dark or dark-dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving thephase of cyclic gene expressionIn the SCN unaffected.
Journal ArticleDOI

A Serum Shock Induces Circadian Gene Expression in Mammalian Tissue Culture Cells

TL;DR: The treatment of cultured rat-1 fibroblasts or H35 hepatoma cells with high concentrations of serum induces the circadian expression of various genes whose transcription also oscillates in living animals, and thus mimics light-induced immediate-early gene expression in the suprachiasmatic nucleus.
Journal ArticleDOI

Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

TL;DR: It is hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.
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