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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 Clock
19 mutant mice selectively
bred to synthesize melatonin. Homozygous melatonin-proficient
Clock
19 mutant mice
(Clock
19/
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
Clock
19/
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 Clock
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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