The tau mutation in the Syrian hamster differentially reprograms the circadian clock in the SCN and peripheral tissues

J. Dey, A. J F Carr, F. R A Cagampang, A. S. Semikhodskii, A. S I Loudon, M. H. Hastings, E. S. Maywood

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The hypothalamic suprachiasmatic nuclei (SCN), the principal circadian oscillator in mammals, are synchronized to the solar day by the light-dark cycle, and in turn, they coordinate circadian oscillations in peripheral tissues. The tau mutation in the Syrian hamster is caused by a point mutation leading to a deficiency in the ability of Casein Kinase 1ε to phosphorylate its targets, including circadian PER proteins. How this accelerates circadian period in neural tissues is not known, nor is its impact on peripheral circadian oscillators established. We show that this mutation has no effect on per mRNA expression nor the nuclear accumulation of PER proteins in the SCN. It does, however, accelerate the clearance of PER proteins from the nucleus to an extent sufficient to explain the shortened circadian period of behavioral rhythms. The mutation also has novel, unanticipated consequences for circadian timing in the periphery, including tissue-specific phase advances and/or reduced amplitude of circadian gene expression. The results suggest that the tau mutation accelerates a specific phase, during mid-late subjective night of the SCN circadian feedback loop, rather than cause a global compression of the entire cycle. This reprogrammed, output from the clock is associated with peripheral desynchrony, which in turn could account for impaired growth and metabolic efficiency of the mutant. © 2005 Sage Publications.
    Original languageEnglish
    Pages (from-to)99-110
    Number of pages11
    JournalJournal of Biological Rhythms
    Volume20
    Issue number2
    DOIs
    Publication statusPublished - Apr 2005

    Keywords

    • Casein kinase 1ε immunocytochemistry
    • Circadian period
    • In situ hybridization
    • PER proteins
    • Period gene

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