tau Mutation in the Syrian Hamster Differentially Reprograms the Circadian Clock in the SCN and Peripheral Tissues

• Published in: Journal of biological rhythms 2005-04, Vol.20 (2), p.99-110
• Main Authors: Dey, J, Carr, A.-J. F, Cagampang, F. R. A, Semikhodskii, A. S, Loudon, A. S. I, Hastings, M. H, Maywood, E. S
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Base Sequence; Biological clocks; Biological Clocks - physiology; Casein; Casein Kinase 1 epsilon - genetics; Casein Kinase 1 epsilon - metabolism; Cell Cycle Proteins; Circadian Rhythm; Circadian rhythms; Compression; Corpus Striatum - metabolism; Cricetinae; DNA Primers; Feedback loops; Gene expression; Gene mutations; Genetic aspects; Hypothalamus; Immunohistochemistry; In Situ Hybridization; Mammals; Mesocricetus; Motor Cortex - metabolism; Mutation; Myocardium - metabolism; Nuclear Proteins - genetics; Nuclei; Oscillators; Period Circadian Proteins; Point Mutation; Proteins; RNA, Messenger - genetics; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic Nucleus - physiology; tau Proteins - genetics; Tissues; Transcription Factors - genetics
• ISSN: 0748-7304; 1552-4531
• DOI: 10.1177/0748730404274264

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 1[epsilon] 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.