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A tunable artificial circadian clock in clock-defective mice

Author

Listed:
  • 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
    Korea Advanced Institute of Science and Technology)

  • Rongmin Chen

    (Program in Neuroscience, College of Medicine, Florida State University
    Present address: Interdepartmental Neuroscience Program, Yale University PO Box 208020, 333 Cedar Street, New Haven, Connecticut 06520-8056, USA.)

  • 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)

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.

Suggested Citation

  • Matthew D’Alessandro & Stephen Beesley & Jae Kyoung Kim & Rongmin Chen & Estela Abich & Wayne Cheng & Paul Yi & Joseph S. Takahashi & Choogon Lee, 2015. "A tunable artificial circadian clock in clock-defective mice," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9587
    DOI: 10.1038/ncomms9587
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