title: Altered phase-relationship between peripheral oscillators and environmental time in Cry1 or Cry2 deficient mouse models for early and late chronotypes.
abstract: The mammalian circadian system is composed of a light-entrainable central clock in the suprachiasmatic nuclei (SCN) of the brain and peripheral clocks in virtually any other tissue. It allows the organism to optimally adjust metabolic, physiological and behavioral functions to the physiological needs it will have at specific time of the day. According to the resonance theory, such rhythms are only advantageous to an organism when in tune with the environment, which is illustrated by the adverse health effects originating from chronic circadian disruption by jetlag and shift work. Using short-period Cry1 and long-period Cry2 deficient mice as models for morningness and eveningness, respectively, we explored the effect of chronotype on the phase relationship between the central SCN clock and peripheral clocks in other organs. Whereas the behavioral activity patterns and circadian gene expression in the SCN of light-entrained Cry1(-/-) and Cry2(-/-) mice largely overlapped with that of wild type mice, expression of clock and clock controlled genes in liver, kidney, small intestine, and skin was shown to be markedly phase-advanced or phase-delayed, respectively. Likewise, circadian rhythms in urinary corticosterone were shown to display a significantly altered phase relationship similar to that of gene expression in peripheral tissues. We show that the daily dissonance between peripheral clocks and the environment did not affect the lifespan of Cry1(-/-) or Cry2(-/-) mice. Nonetheless, the phase-shifted peripheral clocks in light-entrained mice with morningness and eveningness-like phenotypes may have implications for personalized preventive and therapeutic (i.e. chronomodulation-based) health care for people with early and late chronotypes.
authors.affiliation: Department of Genetics, Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Eugin
authors.initials: E
authors.lastname: Destici
authors.affiliation: Department of Genetics, Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Jacobs
authors.affiliation: Department of Genetics, Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Filippo
authors.initials: F
authors.lastname: Tamanini
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Loos
authors.affiliation: Department of Genetics, Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Gijsbertus T J
authors.initials: GT
authors.lastname: van der Horst
authors.affiliation: Department of Genetics, Center for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Oklejewicz
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes / Q000172:deficiency* / Q000235:genetics; D004777:Environment; D005260:Female; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
chemical_list: D056930:ARNTL Transcription Factors; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins