Skip to main content
Log in

Effects of constant light on circadian rhythmicity in mice lacking functional cry genes: dissimilar from per mutants

  • Original Paper
  • Published:
Journal of Comparative Physiology A Aims and scope Submit manuscript

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 (τ) 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 τ 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

LL:

Constant light

DD:

Constant dark

τ:

Circadian period

LD:

Light-dark cycle

SNR:

Signal to noise ratio

References

  • Abraham D, Dallmann R, Steinlechner S, Albrecht U, Eichele G, Oster H (2006) Restoration of circadian rhythmicity in circadian clock-deficient mice in constant light. J Biol Rhythms 21(3):169–176

    Article  PubMed  CAS  Google Scholar 

  • Aschoff J (1960) Exogenous and endogenous components in circadian rhythms. Cold Spring Harb Symp quant Biol 25:11–28

    PubMed  CAS  Google Scholar 

  • Aschoff J (1964) Die Tagesperiodik Licht- und Dunkelaktiver Tiere. Rev Suisse Zoologie 71:528–558

    Google Scholar 

  • Aschoff J (1979) Circadian rhythms: Influences of internal and external factors on the period measured in constant conditions. Z Tierpsychol 49:225–249

    PubMed  CAS  Google Scholar 

  • Aschoff J, Figala J, Pöppel E (1973) Circadian rhythms of locomotor activity in the golden hamster (Mesocricetus auratus) measured with two different techniques. J Comp Physiol Psych 85:20–28

    Article  CAS  Google Scholar 

  • Bae K, Jin X, Maywood ES, Hastings MH, Reppert SM, Weaver DR (2001) Differential functions of mPer1, mPer2 and mPer3 in the SCN circadian clock. Neuron 30:525–536

    Article  PubMed  CAS  Google Scholar 

  • Daan S, Damassa D, Pittendrigh CS, Smith ER (1975) An effect of castration and testosterone replacement on a circadian pacemaker in mice (Mus musculus). Proc Natl Acad Sci-Biol 72:3744–3747

    Article  CAS  Google Scholar 

  • Daan S, Pittendrigh CS (1976) A functional analysis of circadian pacemakers in nocturnal rodents III. Heavy water and constant light: homeostasis of frequency? J Comp Physiol A 106:267–290

    Article  Google Scholar 

  • Daan S, Albrecht U, van-der-Horst GTJ, Ilnerová H, Roenneberg T, Wehr TA, Schwartz WJ (2001) Assembling a clock for all seasons: are there M and E oscillators in the genes? J Biol Rhythms 16:105–116

    Article  PubMed  CAS  Google Scholar 

  • King DP, Takahashi JS (2000) Molecular genetics of circadian rhythms in Mammals. Annu Rev Neurosci 23:713–742

    Article  PubMed  CAS  Google Scholar 

  • Kume K, Zylka MJ, Sriram S, Shearman LP, Weaver DR, Jin X, Maywood ES, Hastings MH, Reppert SM (2004) mCry1 and mCry2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98(2):193–205

    Article  Google Scholar 

  • Mrosovsky N (2001) Further characterisation of the phenotype of mCry1/mCry2-deficient mice. Chronobiol Int 18:613–625

    Article  PubMed  CAS  Google Scholar 

  • Oster H, Baeriswyl S, Van der Horst GTJ, Albrecht U (2003) Loss of circadian rhythmicity in aging mPer1-/-mCry2-/- mutant mice. Genes & Dev 17:1366–1379

    Article  CAS  Google Scholar 

  • Pittendrigh CS, Daan S (1976) A functional analysis of circadian pacemakers in nocturnal rodents V. Pacemaker structure: a clock for all seasons. J Comp Physiol 106:333–355

    Article  Google Scholar 

  • Ruf T (1999) The lomb-scargle periodogram in biological rhythm research: analysis of incomplete and unequally spaced time-series. Biol Rhythm Res 30:178–201

    Article  Google Scholar 

  • Shearman LP, Sriram S, Weaver DR, Maywood ES, Chaves I, Zheng B, Kume K, Lee CC, van der Horst GTJ, Hastings MH, Reppert SM (2000) Interacting molecular loops in the mammalian circadian clock. Science 288:1013–1019

    Article  PubMed  CAS  Google Scholar 

  • Sokolove PG, Bushell WN (1978) The chi square periodogram: its utility for analysis of circaidan rhythms. J Theor Biol 72:131–160

    Article  PubMed  CAS  Google Scholar 

  • Spoelstra K, Oklejewicz M, Daan S (2002) Restoration of self-sustained circadian rhythmicity by the Clock allele in mice in constant illumination. J Biol Rhythms 17:520–525

    Article  PubMed  CAS  Google Scholar 

  • Spoelstra K, Albrecht U, Van der Horst GTJ, Brauer V, Daan S (2004) Phase responses to light pulses in mice lacking functional per or cry genes. J biol Rhythms 19:518–529

    Article  PubMed  CAS  Google Scholar 

  • Steinlechner S, Jacobmeier B, Scherbarth F, Dernbach H, Kruse F, Albrecht U (2002) Robust circadian rhythmicity of Per1 and Per2 mutant mice in constant light, and dynamics of Per1 and Per2 gene expression under long and short photoperiods. J Biol Rhythms 17:202–209

    Article  PubMed  CAS  Google Scholar 

  • Turek FW (1989) Effects of stimulated physical activity on the circadian pacemaker of vertebrates. J Biol Rhythms 4:135–147

    Article  PubMed  CAS  Google Scholar 

  • Van Gelder RN, Wee R, Lee JA, Tu DC (2003) Reduced pupillary light responses in mice lacking cryptochromes. Science 299:222

    Article  PubMed  Google Scholar 

  • Van Gelder RN (2005) Nonvisual ocular photoreception in the mammal. Methods enzymol 393:746–755

    Article  PubMed  Google Scholar 

  • Van der Horst GTJ, Muijtjens M, Kobayashi K, Takano R, Kanno S, Takao M, de Wit J, Verkerk A, Eker APM, van Leenen D, Buijs R, Bootsma D, Hoeijmakers JHJ, Yasui A (1999) Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398:627–630

    Article  PubMed  Google Scholar 

  • White L, Ringo J, Dowse H (1992) A circadian clock of Drosophila: effects of deuterium oxide and mutations at the period locus. Chronobiol Int 9:250–259

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Toh KL, Jones CR, Shin J-Y, Fu Y-H, Ptáček LJ (2007) Modelling of a human circadian mutation yields insight in clock regulation by PER2. Cell 128:59–70

    Article  PubMed  CAS  Google Scholar 

  • Zheng B, Larkin DW, Albrecht U, Sun ZS, Sage M, Eichele G, Lee CC, Bradley A (1999) The mPer2 gene encodes a functional component of the mammalian circadian clock. Nature 400:169–173

    Article  PubMed  CAS  Google Scholar 

  • Zheng B, Albrecht U, Kaasik K, Sage M, Lu W, Vaishnav S, Li Q, Sun ZS, Eichele G, Bradley A, Lee CC (2001) Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Cell 105:683–694

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Our work is supported by the EC’s 5th framework project BRAINTIME (QLRT-2001-01829) and the 6th Framework Project EUCLOCK (No. 018741). We are grateful to Dr. Urs Albrecht and Dr. Bert van der Horst for the original stocks of mPer mutants and mCry mutants, respectively. We thank Gerard J. F. Overkamp for expert technical support, and several reviewers for constructive comments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kamiel Spoelstra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spoelstra, K., Daan, S. Effects of constant light on circadian rhythmicity in mice lacking functional cry genes: dissimilar from per mutants. J Comp Physiol A 194, 235–242 (2008). https://doi.org/10.1007/s00359-007-0301-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00359-007-0301-3

Keywords

Navigation