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Am J Physiol Regul Integr Comp Physiol 284: R1231-R1240, 2003. First published January 9, 2003; doi:10.1152/ajpregu.00697.2002
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Vol. 284, Issue 5, R1231-R1240, May 2003

Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation

David J. Kennaway, Athena Voultsios, Tamara J. Varcoe, and Robert W. Moyer

Department of Obstetrics and Gynaecology, University of Adelaide Medical School, Adelaide, South Australia 5005, Australia

Melatonin and wheel-running rhythmicity and the effects of acute and chronic light pulses on these rhythms were studied in ClockDelta 19 mutant mice selectively bred to synthesize melatonin. Homozygous melatonin-proficient ClockDelta 19 mutant mice (ClockDelta 19/Delta 19-MEL) produced melatonin rhythmically, with peak production 2 h later than the wild-type controls (i.e., just before lights on). By contrast, the time of onset of wheel-running activity occurred within a 20-min period around lights off, irrespective of the genotype. Melatonin production in the mutants spontaneously decreased within 1 h of the expected time of lights on. On placement of the mice in continuous darkness, the melatonin rhythm persisted, and the peak occurred 2 h later in each cycle over the first two cycles, consistent with the endogenous period of the mutant. This contrasted with the onset of wheel-running activity, which did not shift for several days in constant darkness. A light pulse around the time of expected lights on followed by constant darkness reduced the expected 2-h delay of the melatonin peak of the mutants to ~1 h and advanced the time of the melatonin peak in the wild-type mice. When the ClockDelta 19/Delta 19-MEL mice were maintained in a skeleton photoperiod of daily 15-min light pulses, a higher proportion entrained to the schedule (57%) than melatonin-deficient mutants (9%). These results provide compelling evidence that mice with the ClockDelta 19 mutation express essentially normal rhythmicity, albeit with an underlying endogenous period of 26-27 h, and they can be entrained by brief exposure to light. They also raise important questions about the role of Clock in rhythmicity and the usefulness of monitoring behavioral rhythms compared with hormonal rhythms.

circadian; pineal gland; Clock genes; entrainment


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