A tunable artificial circadian clock in clock-defective mice

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Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for biological oscillators, but have limited similarity to physiological pathways. Here we report the generation of an artificial, mammalian circadian clock in vivo, capable of generating robust, tunable circadian rhythms. In mice deficient in Per1 and Per2 genes (thus lacking circadian rhythms), we artificially generate PER2 rhythms and restore circadian sleep/wake cycles with an inducible Per2 transgene. Our artificial clock is tunable as the period and phase of the rhythms can be modulated predictably. This feature, and other design principles of our work, might enhance the study and treatment of circadian dysfunction and broader aspects of physiology involving biological oscillators.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2015-11
Language
English
Article Type
Article
Keywords

CASEIN KINASE 1; DESIGN PRINCIPLES; PERIOD HOMOLOGS; MAMMALIAN CLOCK; CKI-EPSILON; LIGHT; OSCILLATOR; RHYTHMS; PROTEIN; MOUSE

Citation

NATURE COMMUNICATIONS, v.6

ISSN
2041-1723
DOI
10.1038/ncomms9587
URI
http://hdl.handle.net/10203/205546
Appears in Collection
MA-Journal Papers(저널논문)
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