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Updated: Jun 27, 2026
The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression
Published on: July 24, 2018
Molecular clocks in mouse skin
Miki Tanioka1, Hiroyuki Yamada, Masao Doi
1Division of Dermatology, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
Clock genes in the skin exhibit day-night changes in expression; however, whether these changes are brought by external light or intrinsic mechanisms is unclear. In this study, we demonstrated that expression of the clock and clock-controlled genes showed robust rhythms in mouse skin under constant dark conditions, whereas these rhythms were completely lost in Cry1/Cry2 knockout mice lacking a molecular clock. At the cellular level, the main oscillatory protein in the mammalian molecular clock, PER2, was expressed in the nuclei of keratinocytes in the epidermis and hair follicles, with expression peaking at CT16 (subjective dusk), 4-8 hours after expression of its mRNA. These expression patterns in the skin stopped after the ablation of the central clock in the suprachiasmatic nucleus (SCN), which was not recovered even in animals housed in 12 hour-light/12 hour-dark conditions. These findings demonstrate that the intrinsic oscillating molecular clock exists in the epidermis, and that signaling from the SCN is essential for the maintenance of the epidermal clock, and cannot be compensated by external light.
Insights
Skin clock genes show daily rhythms driven by an intrinsic molecular clock, not just light. This internal clock in skin cells is crucial and relies on signals from the brain's central clock.
Area of Science:
- Chronobiology
- Dermatology
- Molecular Biology
Background:
- Skin cells exhibit daily rhythms in gene expression.
- The drivers of these circadian rhythms (external light vs. internal mechanisms) remain unclear.
Purpose of the Study:
- To investigate the intrinsic mechanisms driving circadian rhythms in mouse skin.
- To determine the role of the suprachiasmatic nucleus (SCN) and external light in maintaining skin circadian rhythms.
Main Methods:
- Analysis of clock gene expression in mouse skin under constant darkness.
- Assessment of skin circadian rhythms in Cry1/Cry2 knockout mice lacking a molecular clock.
- Examination of PER2 protein localization and timing in epidermal keratinocytes.
- Investigation of skin clock gene expression following SCN ablation.
Main Results:
- Robust circadian rhythms in clock gene expression were observed in mouse skin under constant dark conditions.
- These rhythms were abolished in mice lacking the core molecular clock components (Cry1/Cry2 knockout).
- PER2 protein rhythmically localized to the nuclei of epidermal and hair follicle keratinocytes.
- Skin circadian rhythms ceased upon SCN ablation and were not restored by standard light-dark cycles.
Conclusions:
- The epidermis possesses an intrinsic, self-sustaining molecular clock.
- Signaling from the central SCN clock is essential for maintaining skin circadian rhythms.
- External light cues cannot compensate for the loss of SCN signaling in regulating the skin clock.
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