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Effect of ultradian light-dark cycles on the transcriptome of mice carying a human Per3 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) M-NM-8 power during wakefulness and M-NM-4 power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in M-NM-4 power, but the Per34/4 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. Mice were kept under 3.5h light- 3.5 hours dark cycles and samples were collected in the 17th light cycle Boxhill represents Per35/5 mice and Coach represents Per34/4 mice. A total of 30 samples comprizing 30 mice

ORGANISM(S): Mus musculus

SUBMITTER: Emma Laing 

PROVIDER: E-GEOD-55495 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Hasan Sibah S   van der Veen Daan R DR   Winsky-Sommerer Raphaelle R   Hogben Alexandra A   Laing Emma E EE   Koentgen Frank F   Dijk Derk-Jan DJ   Archer Simon N SN  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20140227 6


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  ...[more]

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