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Effects of constant light on circadian rhythmicity in mice lacking functional cry genes: dissimilar from per mutants
1Department of Ecology & Evolutionary Biology, Princeton University, 229 Guyot Hall, Washington Road, Princeton, NJ, 08544, USA. KSpoelst@princeton.edu
Abstract:
Mutations in each of the genes mPer1, mPer2, mCry1 and mCry2 separately cause deviations from the wild type circadian system. Differences between these mutant strains have inspired the hypothesis that the duality of circadian genes (two mPer and two mCry genes involved) is related to the existence of two components in the circadian oscillator (Daan et al., J Biol Rhythms 16:105-116, 2001). We tested the predictions from this theory that the circadian period (tau) lengthens under constant illumination (LL) in mCry1 and mPer1 mutant mice, while it shortens in mCry2 and mPer2 mutants. mCry1 ( -/- ) and mCry2 ( -/- ) knockout mice both consistently increased tau with increasing light intensity, as did wild type mice. With increasing illumination, rhythmicity is reduced in mCry1, mCry2 and mPer1, but not in mPer2 deficient mice. Results for mPer mutant mice are in agreement with data reported on these strains earlier by Steinlechner et al. (J Biol Rhythms 17:202-209, 2002), and also with the predictions from the model. The increase in cycle length of the circadian system by light in the mCry2 deficient mice violates the predictions. The model is thereby rejected: the mCry genes do not play a differential role, although the opposite responses of mPer mutants to light remain consistent with a functional Evening-Morning differentiation.
Insights
Circadian rhythm research in mutant mice shows that while mPer genes differentiate light responses, mCry genes do not, challenging the dual-oscillator model of circadian rhythms.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- The circadian system relies on interacting genes, including mPer and mCry families.
- A dual-oscillator model proposes distinct roles for mPer and mCry gene pairs in circadian rhythm regulation.
- Previous studies suggest separate mutations in mPer1, mPer2, mCry1, and mCry2 alter the wild-type circadian system.
Purpose of the Study:
- To test the dual-oscillator model's predictions regarding circadian period (tau) responses to constant light (LL) in mPer and mCry mutant mice.
- To investigate the differential roles of mPer and mCry genes in the circadian system's light-dependent regulation.
Main Methods:
- Utilized mCry1 (-/-), mCry2 (-/-), mPer1, and mPer2 knockout mouse models.
- Measured circadian period (tau) and rhythmicity under varying constant illumination (LL) intensities.
- Compared mutant mouse responses to wild-type controls and theoretical model predictions.
Main Results:
- mCry1 (-/-) and mCry2 (-/-) mice, similar to wild types, increased tau with higher light intensity.
- Rhythmicity decreased with increasing light in mCry1, mCry2, and mPer1 mutants, but not in mPer2 mutants.
- mCry2 mutant mice exhibited an unexpected increase in cycle length under light, contradicting model predictions.
Conclusions:
- The mCry genes do not play differential roles in the circadian system's light response, refuting the dual-oscillator model.
- Opposite light responses in mPer mutants support a functional distinction between Evening and Morning oscillators.
- Further research is needed to fully elucidate the complex interplay of circadian genes and light entrainment.
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