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Circadian rhythms in behavior, metabolism, and physiology are based upon transcriptional/translational feedback loops involving a core set of clock genes that interact to regulate their own expression. In mammals, the SCN is the site of a master biological clock regulating circadian locomotor rhythms. The products of the clock genes mPer1, mPer2, mCry1, and mCry2 form essential components of both negative and positive elements within the SCN oscillator. The primary aims of this study were to examine clock gene abundance under longterm LL in an attempt to provide molecular correlates of the lengthened tau and daily phase delays described by Aschoff's rule. Wheel-running behavior was recorded from mice maintained in either DD or LL for 50 days. The abundance of the clock genes mPer1, mPer2, mCry1, and mCry2 and their protein products was then examined (every approximately 4 h) within the SCN using in situ hybridization and immunocytochemistry. Under LL conditions, mPer1, mPer2, mCry1, and mCry2 messages remained rhythmic, although the waveform of mCry2 was altered compared to DD. In LL, mPER1, mCRY1, and mCRY2 protein levels were also rhythmic and comparable to the patterns observed in DD. However, mPER2 is elevated and constitutively expressed under LL. Thus, rhythmic expression of these clock genes is not dependent on the rhythmic production of mPER2, and the acute up-regulation of mPer1 and mPer2 described for short (nonparametric) light pulses is not sustained under LL conditions. These findings suggest that mPER2 is important for the generation of phase delays in the molecular clockwork, providing a possible molecular explanation for Aschoff's rule: LL lengthens the circadian period by inhibiting the degeneration of mPER2, and constitutively elevated levels of mPER2 enhance the phase-delaying limb of the molecular oscillator.

Original publication

DOI

10.1177/0748730404272858

Type

Journal article

Journal

J Biol Rhythms

Publication Date

02/2005

Volume

20

Pages

3 - 14

Keywords

Animals, Cell Cycle Proteins, Circadian Rhythm, Gene Expression Regulation, Immunohistochemistry, In Situ Hybridization, Light, Male, Mice, Mice, Inbred C3H, Nuclear Proteins, Period Circadian Proteins, RNA, Messenger, Suprachiasmatic Nucleus, Transcription Factors