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

TLDR

Circadian rhythms are governed by the suprachiasmatic nucleus, which is traditionally considered essential for peripheral tissue rhythms. PERIOD2::LUCIFERASE imaging demonstrates that peripheral tissues sustain self‑sustained circadian oscillations for over 20 cycles in isolation, display tissue‑specific periods and phases, and remain rhythmic after SCN lesions—though such lesions cause phase desynchrony—suggesting organ‑level synchronizers independent of the SCN.

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 mPer2 Luciferase 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.