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Establishing a Device for Sleep Deprivation in Mice
Published on: September 22, 2023
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A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat
Sibah Hasan1, Daan R van der Veen1, Raphaelle Winsky-Sommerer1
1Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK; and.
Summary
The PER3 gene polymorphism influences sleep, affecting how the body responds to sleep loss. Mice with a specific PER3 gene variant showed stronger sleep regulation and better recovery after sleep deprivation.
Area of Science:
- Chronobiology
- Sleep Science
- Genetics
Background:
- A variable-number tandem-repeat (VNTR) polymorphism in the human PER3 gene influences sleep timing and homeostatic responses.
- This polymorphism is primate-specific and involves 4 or 5 repeats of a 54-nucleotide sequence.
Purpose of the Study:
- To investigate the impact of the PER3 VNTR polymorphism on circadian rhythmicity and sleep homeostasis.
- To assess the effects of this polymorphism in a mouse model under baseline and sleep-deprived conditions.
Main Methods:
- Introduction of the human PER3 VNTR polymorphism into mice.
- Assessment of circadian behavior and sleep parameters at baseline and after 12 hours of sleep deprivation (SD).
- Microarray analysis of hypothalamic and cortical gene expression.
Main Results:
- Mice with the Per3(5/5) genotype exhibited heightened electrophysiological responses to SD, indicated by increased EEG θ power during wakefulness and δ power during sleep.
- Per3(5/5) mice demonstrated full compensation for SD-induced δ power deficits during recovery, unlike Per3(4/4) and wild-type mice.
- Differential expression of sleep homeostasis-related genes (e.g., Homer1, Ptgs2, Kcna2) was observed, while circadian clock genes remained unaffected.
Conclusions:
- The PER3 VNTR polymorphism modulates the sleep homeostatic response to sleep deprivation.
- Circadian parameters were not significantly influenced by the PER3 VNTR polymorphism in this model.
- Findings support the hypothesis that the PER3 VNTR polymorphism affects sleep homeostasis rather than core circadian timing.
