TY - JOUR
T1 - Phase responses to light pulses in mice lacking functional per or cry genes
AU - Spoelstra, Kamiel
AU - Albrecht, Urs
AU - Van Der Horst, Gijsbertus T.J.
AU - Brauer, Verena
AU - Daan, Serge
PY - 2004/12
Y1 - 2004/12
N2 - 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 mPer1Brdm1 and mPer2Brdm1 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, mPer2Brdm1 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 mPer1Brdm1 mutant and wild-type PRC (i.e., less delayed and more advanced) at most circadian phases. The mPer1Brdm1 mutant PRC was not distinguishable from the wild-type PRC. The mCry2-/- mice showed much smaller phase delays than did mCry1-/- mice in the subjective evening (delay phase). In general, mPer2Brdm1 mutant mice were more accelerated by light compared to mPer1Brdm1 and wild-type control mice, whereas mCry1-/- mice were more delayed by light than were mCry2-/- mice.
AB - 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 mPer1Brdm1 and mPer2Brdm1 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, mPer2Brdm1 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 mPer1Brdm1 mutant and wild-type PRC (i.e., less delayed and more advanced) at most circadian phases. The mPer1Brdm1 mutant PRC was not distinguishable from the wild-type PRC. The mCry2-/- mice showed much smaller phase delays than did mCry1-/- mice in the subjective evening (delay phase). In general, mPer2Brdm1 mutant mice were more accelerated by light compared to mPer1Brdm1 and wild-type control mice, whereas mCry1-/- mice were more delayed by light than were mCry2-/- mice.
KW - Circadian clock
KW - Cry1
KW - Cry2
KW - Per1
KW - Per2
KW - Phase resetting
KW - PRC
U2 - 10.1177/0748730404268122
DO - 10.1177/0748730404268122
M3 - Article
C2 - 15523113
AN - SCOPUS:8644249076
SN - 0748-7304
VL - 19
SP - 518
EP - 529
JO - Journal of Biological Rhythms
JF - Journal of Biological Rhythms
IS - 6
ER -