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Science 28 April 2000:
Vol. 288. no. 5466, pp. 682 - 685
DOI: 10.1126/science.288.5466.682
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Reports

Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

Shin Yamazaki, 1* Rika Numano, 2* Michikazu Abe, 1* Akiko Hida, 2 Ri-ichi Takahashi, 3 Masatsugu Ueda, 3 Gene D. Block, 1 Yoshiyuki Sakaki, 2 Michael Menaker, 1dagger Hajime Tei 2dagger

In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We 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.

1 NSF Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22903-2477, USA.
2 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
3 Y.S. New Technology Institute Inc., 519 Shimoishibashi, Ishibashi-machi, Tochigi, 329-0500, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: mm7e{at}virginia.edu (M.M.) or tei{at}ims.u-tokyo.ac.jp (H.T.).

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