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A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.

Hasan, S, van der Veen, DR, Winsky-Sommerer, R, Hogben, A, Laing, EE, Koentgen, F, Dijk, DJ and Archer, SN (2014) A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism. FASEB J.

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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.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Hasan, SUNSPECIFIEDUNSPECIFIED
van der Veen, DRUNSPECIFIEDUNSPECIFIED
Winsky-Sommerer, RUNSPECIFIEDUNSPECIFIED
Hogben, AUNSPECIFIEDUNSPECIFIED
Laing, EEUNSPECIFIEDUNSPECIFIED
Koentgen, FUNSPECIFIEDUNSPECIFIED
Dijk, DJUNSPECIFIEDUNSPECIFIED
Archer, SNUNSPECIFIEDUNSPECIFIED
Date : 5 March 2014
Identification Number : 10.1096/fj.13-240135
Uncontrolled Keywords : EEG, circadian, clock genes, sleep deprivation
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 01 May 2014 12:49
Last Modified : 09 Jun 2014 13:57
URI: http://epubs.surrey.ac.uk/id/eprint/805296

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