title: A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.
abstract: In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) θ power during wakefulness and δ power during sleep, were greater in the Per3(5/5) mice. During recovery, the Per3(5/5) mice fully compensated for the SD-induced deficit in δ power, but the Per3(4/4) and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
authors.forename: Sibah
authors.initials: S
authors.lastname: Hasan
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
authors.forename: Daan R
authors.initials: DR
authors.lastname: van der Veen
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Winsky-Sommerer
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hogben
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
authors.forename: Emma E
authors.initials: EE
authors.lastname: Laing
authors.affiliation: Ozgene Pty. Ltd., Bentley, Western Australia, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Koentgen
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
authors.forename: Derk-Jan
authors.initials: DJ
authors.lastname: Dijk
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and simon.archer@surrey.ac.uk.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Archer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D002540:Cerebral Cortex / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D003624:Darkness; D015536:Down-Regulation; D004569:Electroencephalography; D005260:Female; D063990:Gene Ontology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008027:Light; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018598:Minisatellite Repeats; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins
keywords: EEG; circadian; clock genes; sleep deprivation