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Phase responses to light pulses in mice lacking functional per or cry genes
Kamiel Spoelstra1, Urs Albrecht, Gijsbertus T J van der Horst
1Zoological Laboratory, University of Groningen, The Netherlands. K.Spoelstra@biol.rug.nl
Journal of Biological Rhythms
|November 4, 2004
Summary
Circadian rhythm gene deletions in mice reveal distinct light response patterns. Mutant mice show altered phase shifts, with mPer2 mutants exhibiting accelerated rhythms and mCry1 mutants showing greater delays, impacting overall circadian timing.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- The circadian system regulates daily biological rhythms, crucial for organismal health.
- Core clock genes, including Period (Per) and Cryptochrome (Cry), are essential for circadian rhythmicity.
- Understanding the specific roles of these genes in light-induced phase resetting is vital.
Purpose of the Study:
- To investigate the phase-resetting properties of the mouse circadian system.
- To determine the impact of targeted gene deletions in mCry1, mCry2, mPer1, and mPer2 on light-induced phase shifts.
- To characterize the phase response curves (PRCs) of these mutant mouse strains.
Main Methods:
- Two experiments were conducted using genetically modified mice (mCry1-/-, mCry2-/-, mPer1(Brdm1), mPer2(Brdm1)) and wild-type controls.
- Mice were exposed to 15-min light pulses at specific times during entrainment and under free-running conditions in constant darkness.
- Phase shifts were measured, and full phase response curves (PRCs) were generated for each genotype.
Main Results:
- mPer1(Brdm1) mice showed no significant phase advances to late-night light pulses. mPer2(Brdm1) mice frequently became arrhythmic.
- mCry1(-/-) and mCry2(-/-) mice exhibited increased phase delays to early-night light pulses compared to wild types.
- In free-running conditions, mPer2(Brdm1) PRCs indicated greater light acceleration, while mPer1(Brdm1) PRCs were similar to wild types. mCry1(-/-) mice showed larger delays than mCry2(-/-) mice.
Conclusions:
- Distinct roles for mPer2 and mCry1/mCry2 in mediating light-induced circadian phase shifts were identified.
- mPer2 plays a significant role in light-induced acceleration, while mCry1 and mCry2 influence light-induced delays.
- These findings highlight the differential contributions of core clock genes to the plasticity of the mammalian circadian system.