title: Abnormal wake/sleep pattern in a novel gain-of-function model of DISC1.
abstract: Sleep disturbances are common in psychiatric disorders, but the causal relationship between the two and the underlying genetic factors is unclear. The DISC1 gene is strongly linked to mood disorders and schizophrenia in a Scottish pedigree. In an earlier study we found a sleep homeostasis disturbance in a Drosophila model overexpressing wild-type human DISC1. Here we aimed to explore the relationship between sleep and the DISC1 gene in a mammalian model, a novel transgenic mouse model expressing full-length human DISC1. We assessed circadian rhythms by monitoring wheel running activity under normal 24-h light:dark conditions and in constant darkness and found the DISC1 mice to have normal circadian photoentrainment and normal intrinsic circadian period. We also assessed sleep duration and quality in the DISC1 mice and found that they were awake longer than wild-type controls at baseline with a tendency for lower rebound of delta activity during recovery from a short sleep deprivation. Thus we suggest that DISC1 may be involved in sleep regulation.
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, United States. Electronic address: hjaarop1@jhmi.edu.
authors.forename: Hanna
authors.initials: H
authors.lastname: Jaaro-Peled
authors.affiliation: Department of Biology, Johns Hopkins University, United States.
authors.forename: Cara
authors.initials: C
authors.lastname: Altimus
authors.affiliation: Department of Biology, Johns Hopkins University, United States.
authors.forename: Tara
authors.initials: T
authors.lastname: LeGates
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, United States.
authors.forename: Tyler
authors.initials: T
authors.lastname: Cash-Padgett
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zoubovsky
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, United States.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hikida
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, United States.
authors.forename: Koko
authors.initials: K
authors.lastname: Ishizuka
authors.affiliation: Department of Biology, Johns Hopkins University, United States. Electronic address: shattar@jhu.edu.
authors.forename: Samer
authors.initials: S
authors.lastname: Hattar
authors.affiliation: Department of Neurosciences, Université de Montréal, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Mongrain
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, United States. Electronic address: asawa1@jhmi.edu.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002940:Circadian Rhythm; D006801:Humans; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins
keywords: Behavior; Circadian rhythms; DISC1; Mouse model; Non rapid eye movement sleep; Rapid eye movement sleep; Sleep homeostasis