MODEL0478895291
type: SBMLModel
parameter: 030930
parameter: 031023
parameter: 030980
rule: 030926
parameter: 031025
parameter: 030965
units def: 460682
parameter: 030942
rule: 030911
parameter: 030977
parameter: 031014
parameter: 030954
parameter: 030968
units def: 460573
parameter: 030989
units def: 460658
parameter: 031001
parameter: 030962
length unit: 222721
area units: area
rule: 030914
parameter: 031013
parameter: 030974
notes: This a model from the article: Modeling the mammalian circadian clock: sensitivity analysis and multiplicity of oscillatory mechanisms. Leloup JC, Goldbeter A. J Theor Biol. 2004 Oct 21;230(4):541-62. 15363675 , Abstract: We extend the study of a computational model recently proposed for the mammalian circadian clock (Proc. Natl Acad. Sci. USA 100 (2003) 7051). The model, based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, and Clock genes, can give rise to sustained circadian oscillations in conditions of continuous darkness. These limit cycle oscillations correspond to circadian rhythms autonomously generated by suprachiasmatic nuclei and by some peripheral tissues. By using different sets of parameter values producing circadian oscillations, we compare the effect of the various parameters and show that both the occurrence and the period of the oscillations are generally most sensitive to parameters related to synthesis or degradation of Bmal1 mRNA and BMAL1 protein. The mechanism of circadian oscillations relies on the formation of an inactive complex between PER and CRY and the activators CLOCK and BMAL1 that enhance Per and Cry expression. Bifurcation diagrams and computer simulations nevertheless indicate the possible existence of a second source of oscillatory behavior. Thus, sustained oscillations might arise from the sole negative autoregulation of Bmal1 expression. This second oscillatory mechanism may not be functional in physiological conditions, and its period need not necessarily be circadian. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark (LD) cycles. Long-term suppression of circadian oscillations by a single light pulse can occur in the model when a stable steady state coexists with a stable limit cycle. The phase of the oscillations upon entrainment in LD critically depends on the parameters that govern the level of CRY p…
parameter: 030951
rule: 030913
parameter: 031029
parameter: 030969
rule: 030922
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units def: 460549
parameter: 030986
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rule: 030907
parameter: 030998
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parameter: 030971
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compartment: 030891
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parameter: 031026
parameter: 030966
parameter: 030983
parameter: 030938
rule: 030910
parameter: 030978
rule: 030920
parameter: 030995
volume units: volume
substance units: substance
parameter: 031002
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parameter: 031004
parameter: 030935
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parameter: 030975
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parameter: 031016
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parameter: 031007
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parameter: 031022
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parameter: 030941
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name: MP

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460585
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031032
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