Abstract
The master circadian clock of mammals resides in the suprachiasmatic nucleus of the hypothalamus (SCN). However, most peripheral organs have also their own clocks generating circadian rhythms in clock and clock-controlled gene expressions. In order to examine the mechanisms by which the master clock regulates the peripheral clocks, we constructed a transgenic mouse line expressing firefly luciferase under the control of clock gene Bmal1 promoter and examined oscillatory mechanisms of the central and peripheral clocks by continuously monitoring bioluminescence of cultured SCN and liver. The oscillation mechanisms are also examined in the peripheral clock model of Rat-1 fibroblasts using the same Bmal1 reporter construct. Rat-1 fibroblasts showed a type 0 phase response curve not only to a brief exposure of dexamethasone but also to vehicle treatment, suggesting that desynchronized cellular oscillators are resynchronized to each other by a single perturbation. Synchronization of a number of peripheral clocks by this method seems to be advantageous for the orchestration of circadian rhythms in physiology and behavior. However, a single peripheral clock responds to multiple mediators with different sensitivities, which may cause internal desynchronization among organs and cells. [Jpn J Physiol 55 Suppl:S54 (2005)]
