public model
Short description

This is model in continous darkness (DD) described in the article Toward a detailed computational model for the mammalian circadian clock

This model features the full interlocked negative and positive regulation of Per,Cry,Bmal and REV-ERBalpha. The model exhibits robust oscillations quite independent of the initial conditions for teh parameters given. Each species is assigned zero as initial value, and the graph started at time=120h.

Simulation results could be reproduced using Copasi 4.0.19(development) and roadRunner online.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.
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To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Related Publication
  • Toward a detailed computational model for the mammalian circadian clock.
  • Leloup JC, Goldbeter A
  • Proceedings of the National Academy of Sciences of the United States of America , 6/ 2003 , Volume 100 , pages: 7051-7056
  • Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, C. P. 231, B-1050 Brussels, Belgium.
  • We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb alpha genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erbalpha and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.
Enuo He

Metadata information

BioModels Database BIOMD0000000021
BioModels Database MODEL1272626224
BioModels Database BIOMD0000000074
PubMed 12775757
Taxonomy Homo sapiens
Curation status
  • Model originally submitted by : Enuo He
  • Submitted: 01-Nov-2006 15:13:11
  • Last Modified: 25-Feb-2015 13:01:01
  • Version: 2 public model Download this version
    • Submitted on: 25-Feb-2015 13:01:01
    • Submitted by: Enuo He
    • With comment: Current version of Leloup2003_CircClock_DD_REV-ERBalpha
  • Version: 1 public model Download this version
    • Submitted on: 01-Nov-2006 15:13:11
    • Submitted by: Enuo He
    • With comment: Original import of Leloup2003_CircClock_DD_REV-ERBalpha
Curator's comment:
(added: 28 Nov 2006, 10:27:39, updated: 28 Nov 2006, 10:27:39)
Supporting figure 8a obtained in RoadRunner.