Phase Responses to Light Pulses in Mice Lacking Functional per or cry Genes

Nov 4, 2004Journal of biological rhythms

Changes in daily activity timing after light exposure in mice without key internal clock genes

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Abstract

mPer2(Brdm1) mutant mice showed greater phase advances in response to light compared to mPer1(Brdm1) mutants and wild-type controls.

mCry1(-/-) and mCry2(-/-) mice exhibited increased phase delays after light exposure in the early subjective night.
mPer1(Brdm1) mice did not exhibit significant phase advances when exposed to light pulses late in the subjective night.
mPer2(Brdm1) mice became arrhythmic too frequently to measure their phase responses reliably.
All genotypes demonstrated phase advances and delays under free-running conditions in constant darkness.
The phase response curve (PRC) of mPer2(Brdm1) mutants was less delayed and more advanced than that of mPer1(Brdm1) mutants and wild-type mice.
mCry2(-/-) mice exhibited smaller phase delays compared to mCry1(-/-) mice in the subjective evening.

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The phase-resetting properties of the circadian system in mice with a functional deletion in mCry1, mCry2, mPer1, or mPer2 were studied in 2 experiments. In experiment 1, mCry1(-/-) and mCry2(-/-) mice as well as mPer1(Brdm1) and mPer2(Brdm1) mutant mice were exposed to 15-min light pulses during the 1st cycle following entrainment, either early (external time [ExT] 20) or late (ExT 4) in the subjective night. In experiment 2, a full PRC was measured for all these strains by exposure to light pulses of the same duration and intensity in free-running conditions in constant darkness. Directly after entrainment (experiment 1), mPer1(Brdm1) animals did not show significant phase advances by a light pulse in the late subjective night (ExT 4), as in the study by Albrecht et al. In the same experiment, mPer2(Brdm1) mice became arrhythmic too frequently to reliably measure their phase responses. Mice with a targeted gene disruption in mCry1 or mCry2 showed increased phase delays compared to wild type after exposure to a light pulse in the early subjective night (ExT 20). Otherwise, phase shifts were not significantly affected. In free run (experiment 2), all genotypes did show phase advances and phase delays. The mPer2(Brdm1) mutant PRC was above the mPer1(Brdm1) mutant and wild-type PRC (i.e., less delayed and more advanced) at most circadian phases. The mPer1(Brdm1) mutant PRC was not distinguishable from the wildtype PRC. The mCry2(-/-) mice showed much smaller phase delays than did mCry1(-/-) mice in the subjective evening (delay phase). In general, mPer2(Brdm1) mutant mice were more accelerated by light compared to mPer1(Brdm1) and wildtype control mice, whereas mCry1(-/-) mice were more delayed by light than were mCry2(-/-) mice.

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Phase Responses to Light Pulses in Mice Lacking Functional per or cry Genes

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