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Updated: Aug 14, 2026
Slice Preparation, Organotypic Tissue Culturing and Luciferase Recording of Clock Gene Activity in the Suprachiasmatic Nucleus
Published on: February 16, 2011
Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock
1Laboratory of Developmental Chronobiology, MassGeneral Hospital for Children, Massachusetts General Hospital, and, Harvard Medical School, 02114, Boston, MA, USA
Abstract:
The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes.
Insights
Disrupting mPer1 or mPer2 genes severely impacted mouse circadian rhythms. Double mutations in mPer1 and mPer2 caused immediate arrhythmicity, highlighting their critical roles in the core circadian clockwork.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- Circadian rhythms are endogenous biological processes that regulate daily cycles.
- The molecular mechanisms underlying circadian rhythmicity involve a complex network of clock genes.
- Mammalian Period (mPer) genes, including mPer1 and mPer2, are key components of the circadian clockwork.
Purpose of the Study:
- To investigate the specific roles of mPer1 and mPer2 in regulating circadian rhythms.
- To determine the contribution of mPer3 to the circadian clockwork.
- To elucidate the functional relationship and compensation between mPer1 and mPer2.
Main Methods:
- Gene disruption in mice to create mPer1, mPer2, and double mutant lines (mPer1/mPer2, mPer1/mPer3, mPer2/mPer3).
- Assessment of locomotor activity rhythms under constant darkness.
- Analysis of clock gene RNA rhythms in the suprachiasmatic nucleus.
- Measurement of PER and CRY1 protein levels.
Main Results:
- Mice with single mPer1 or mPer2 gene disruption exhibited severely disrupted locomotor activity rhythms.
- mPer2 mutant mice showed blunted clock gene RNA rhythms in the suprachiasmatic nucleus, unlike mPer1 deficient mice.
- mPer1/mPer2 double-mutant mice became immediately arrhythmic, indicating essential roles for both genes.
- mPer3 disruption did not significantly alter rhythms beyond the effects of mPer1 or mPer2 disruption.
Conclusions:
- mPER1 and mPER2 are essential for maintaining circadian rhythmicity in mice.
- mPER2 plays a significant role in regulating rhythmic gene expression.
- mPER1's function in rhythmicity is largely dependent on interactions with other clock proteins.
- Partial compensation exists between mPER1 and mPER2, but their combined disruption leads to arrhythmicity.
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