Ueda, Hagiwara, Kitano, 2001

Model Status

This CellML model is known to run in both OpenCell and COR to replicate the published results. The units have been checked and they are consistent.

Model Structure

ABSTRACT: A mechanism for generating circadian rhythms has been of major interest in recent years. After the discovery of per and tim, a model with a simple feedback loop involving per and tim has been proposed. However, it is recognized that the simple feedback model cannot account for phenotypes generated by various mutants. A recent report by Glossop, Lyons and Hardin [Science286, 766 (1999)] on Drosophila suggests involvement of another feedback loop by dClk that is interlocked with per-tim feedback loop. In order to examine whether interlocked feedback loops can be a basic mechanism for circadian rhythms, a mathematical model was created and examined. Through extensive simulation and mathematical analysis, it was revealed that the interlocked feedback model accounts for the observations that are not explained by the simple feedback model. Moreover, the interlocked feedback model has robust properties in oscillations.

The original paper reference is cited below:

Robust oscillations within the interlocked feedback model of Drosophila circadian rhythm, Hiroki R. Ueda, Masatoshi Hagiwara, and Hiroaki Kitano, 2001, Journal of Theoretical Biology, 210, 401-406. PubMed ID: 11403560

The interlocked feedback model of Drosophila circadian rhythm.