title: A tunable artificial circadian clock in clock-defective mice.
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.
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: D'Alessandro
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Beesley
authors.affiliation: Mathematical Biosciences Institute, The Ohio State University, 1735 Neil Avenue, Columbus, Ohio 43210, USA.|Department of Mathematical Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Jae Kyoung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Rongmin
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Estela
authors.initials: E
authors.lastname: Abich
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Yi
authors.affiliation: Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.affiliation: Department of Biomedical Sciences, Program in Neuroscience, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, Florida 32306, USA.
authors.forename: Choogon
authors.initials: C
authors.lastname: Lee
mesh_terms: D000818:Animals; D021081:Chronobiology Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D057906:Circadian Clocks; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056950:Period Circadian Proteins / Q000172:deficiency / Q000235:genetics
chemical_list: C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins