Resetting central and peripheral circadian oscillators in transgenic rats.
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.
Yamazaki
S
S
NSF Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22903-2477, USA.
Numano
R
R
Abe
M
M
Hida
A
A
Takahashi
R
R
Ueda
M
M
Block
G D
GD
Sakaki
Y
Y
Menaker
M
M
Tei
H
H
D000818:Animals; D030801:Animals, Genetically Modified; D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D046508:Culture Techniques; D003624:Darkness; D017930:Genes, Reporter; D008027:Light; D008099:Liver / Q000502:physiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D008156:Luciferases