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Updated: Jan 25, 2026
In Vivo Monitoring of Circadian Clock Gene Expression in the Mouse Suprachiasmatic Nucleus Using Fluorescence Reporters
Published on: July 4, 2018
A Period1 inducer specifically advances circadian clock in mice
Yoshifumi Takahata1,2,3, Yuki Kasashima3, Takuya Yoshioka3
1Department of Genome Editing Research and Development Unit, Graduate School of Dentistry, University of Osaka, Osaka 565-0871, Japan.
A new compound, Mic-628, can rapidly advance the mammalian circadian clock by inducing Period1 (Per1) expression. This offers a potential therapeutic strategy for circadian rhythm disorders caused by jet lag.
Area of Science:
- Chronobiology
- Molecular Biology
- Pharmacology
Background:
- Transmeridian travel disrupts circadian rhythms, particularly when traveling west-to-east, due to difficulties in advancing the internal body clock.
- Previous research suggested transient mammalian Period1 (Per1) induction could advance the clock phase.
Purpose of the Study:
- To identify a specific inducer of Per1 for rapid circadian clock phase advance.
- To investigate the molecular mechanism of action for a novel Per1 inducer, Mic-628.
- To evaluate the efficacy of Mic-628 in accelerating re-entrainment to shifted light-dark cycles in mice.
Main Methods:
- Administration of Mic-628 to mice and assessment of behavioral rhythms.
- Analysis of the interaction between Mic-628 and CRYPTOCHROME1 (CRY1).
- Investigation of Per1 promoter regulation and the role of PER1 in feedback inhibition.
- Mathematical modeling of circadian clock dynamics.
Main Results:
- Mic-628 induced rapid phase advance in mouse behavioral rhythms, irrespective of administration timing.
- Mic-628-treated mice showed significantly faster re-entrainment to phase-advanced light-dark cycles.
- Mic-628 facilitates CLOCK-BMAL1 assembly via CRY1 interaction, leading to specific Per1 induction.
- PER1 repressed Mic-628-driven Per1 induction, with both CRY1 and PER1 fixing the phase of Per1 induction.
Conclusions:
- Mic-628 is a potent inducer of Per1, capable of advancing the circadian clock phase.
- The mechanism involves facilitated CLOCK-BMAL1 assembly and dual regulation by CRY1 and PER1.
- Selective Per gene expression modulation presents a promising therapeutic avenue for circadian rhythm disorders.
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