Leloup2003_CircClock_LD_REV-ERBalpha

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Short description

This is model is according to the paperToward a detailed computational model for the mammalian circadian clock

In this model interlocked negative and positive regulation of Per,Cry,Bmal,REV-ERBalpha genes are all involved.The model is actually robust so the initial conditions are unimportant.We gave every entity zero as initial value,and start the graph at time=132h.

The simulation results in figure 8B can be reproduced by roadRunner online and Copasi. We use a ceiling function to simulate the day-light cycle.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V4)
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.
Contributors
Enuo He

Metadata information

is
BioModels Database MODEL4710748444
BioModels Database BIOMD0000000083
isDerivedFrom
BioModels Database BIOMD0000000021
isDescribedBy
PubMed 12775757
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasVersion
Curation status
Curated
  • Model originally submitted by : Enuo He
  • Submitted: 28-Nov-2006 18:31:09
  • Last Modified: 25-Feb-2015 13:04:16
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 25-Feb-2015 13:04:16
    • Submitted by: Enuo He
    • With comment: Current version of Leloup2003_CircClock_LD_REV-ERBalpha
  • Version: 1 public model Download this version
    • Submitted on: 28-Nov-2006 18:31:09
    • Submitted by: Enuo He
    • With comment: Original import of Leloup2003_CircClock_LD_REV-ERBalpha
Curator's comment:
(added: 21 Apr 2011, 03:44:49, updated: 21 Apr 2011, 03:44:49)
Reproduction of the supplementary figure 8B of the publication. The time course was integrated using Copasi v4.6.33. Only concentrations from time=132 h onwards are shown, and the x axis is reset to 0 at time=132.