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

Seung Hee Yoo, Shin Yamazaki, Phillip L. Lowrey, Kazuhiro Shimomura, Caroline H. Ko, Ethan D. Buhr, Sandra M. Siepka, Hee Kyung Hong, Won Jun Oh, Ook Joon Yoo, Michael Menaker, Joseph S. Takahashi

Research output: Contribution to journalArticle

1426 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5339-5346
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number15
DOIs
StatePublished - Apr 13 2004

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