A tunable artificial circadian clock in clock-defective mice

Matthew D’Alessandro, Stephen Beesley, Jae Kyoung Kim, Rongmin Chen, Estela Abich, Wayne Cheng, Paul Yi, Joseph S. Takahashi and Choogon Lee ()
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Matthew D’Alessandro: Program in Neuroscience, College of Medicine, Florida State University
Stephen Beesley: Program in Neuroscience, College of Medicine, Florida State University
Jae Kyoung Kim: Mathematical Biosciences Institute, The Ohio State University
Rongmin Chen: Program in Neuroscience, College of Medicine, Florida State University
Estela Abich: Program in Neuroscience, College of Medicine, Florida State University
Wayne Cheng: Program in Neuroscience, College of Medicine, Florida State University
Paul Yi: Program in Neuroscience, College of Medicine, Florida State University
Joseph S. Takahashi: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center
Choogon Lee: Program in Neuroscience, College of Medicine, Florida State University

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms9587

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