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‡, and
- Joseph S. Takahashi*,¶,††
- ¶Howard Hughes Medical Institute, *Department of Neurobiology and Physiology, and ∥Center for Functional Genomics, Northwestern University, 2205 Tech Drive, Evanston, IL 60208; ‡National Science Foundation Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22904; †Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea; and **Department of Psychology, University of Toronto, Toronto, ON, Canada M5S 3G3
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Contributed by Joseph S. Takahashi, December 30, 2003
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.
Footnotes
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↵ †† To whom correspondence should be addressed. E-mail: j-takahashi{at}northwestern.edu.
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↵ § Present address: Department of Biological Sciences, Vanderbilt University, Box 1634-B, Nashville, TN 37235-1634.
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This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on April 29, 2003.
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Abbreviations: Per2, Period2; Luc, luciferase; SCN, suprachiasmatic nucleus; ES, embryonic stem; LD12:12, 12-h light/12-h dark cycle; DD, constant darkness; PMT, photomultiplier tube.
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See accompanying Biography on page 5336.
- Copyright © 2004, The National Academy of Sciences
