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Published on: September 27, 2012
Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock
1Department of Anatomy and Brain Science, Kobe University School of Medicine, Kobe 650-0017, Japan. okamurah@kobe-u.ac.jp
Abstract:
Mice lacking mCry1 and mCry2 are behaviorally arrhythmic. As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and mPer2 mRNA levels are constitutively high. These findings indicate that the biological clock is eliminated in the absence of both mCRY1 and mCRY2 (mammalian cryptochromes 1 and 2) and support the idea that mammalian CRY proteins act in the negative limb of the circadian feedback loop. The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals. Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock.
Insights
Mice lacking both mammalian cryptochromes (mCRY1 and mCRY2) lose their biological clock, leading to arrhythmic behavior. However, these cryptochromes are not essential for light-induced clock resetting.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- Circadian rhythms are regulated by molecular feedback loops involving clock genes.
- Mammalian cryptochromes (mCRY1 and mCRY2) are key components of the circadian clock.
- The precise role of mCRY1 and mCRY2 in the negative limb of the feedback loop requires further elucidation.
Purpose of the Study:
- To investigate the function of mCRY1 and mCRY2 in maintaining circadian rhythmicity.
- To determine the role of mCRY1 and mCRY2 in the negative limb of the circadian feedback loop.
- To assess the necessity of mCRY1 and mCRY2 for light-induced phase shifting.
Main Methods:
- Generation and behavioral analysis of mCry1 and mCry2 double-mutant mice.
- Quantitative analysis of mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus and peripheral tissues.
- Assessment of light-induced phase shifting response in mutant mice.
Main Results:
- Mice lacking both mCRY1 and mCRY2 exhibited behavioral arrhythmicity.
- Cyclic expression of mPer1 and mPer2 was abolished, with constitutively high mRNA levels.
- mCRY1 and mCRY2 were found to be dispensable for light-induced phase shifting.
Conclusions:
- Mammalian CRY proteins (mCRY1 and mCRY2) are essential for the operation of the biological clock.
- mCRY1 and mCRY2 function in the negative limb of the circadian feedback loop.
- Light-induced phase shifting of the circadian clock does not require mCRY1 and mCRY2.
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