Parmar2017_Mouse Iron Distribution - Rich and Deficient iron diets (tracer)

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Short description

Mouse Iron Distribution Dynamics

Dynamic model of iron distribution in mice. This model attempts to fit the radioiron tracer data from Lopes et al. 2010 for mice fed iron deficient and rich diets by adjusting the rate of iron intake (vDiet) and the hepcidin synthesis rate (vhepcidin) independently for each experiment. All other parameters are those that provide the best fit for the adequate diet.

This model includes the radioiron tracer species.


Differences in parameter values between deficient, rich, and adequate diets:

Diet vDiet vhepcidin
Adequate 0.00377422 1.7393e-08
Deficient 0 8.54927e-09
Rich 0.00415624 2.30942e-08
Format
SBML (L2V4)
Related Publication
  • Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient.
  • Pedro Mendes
  • BMC systems biology , 5/ 2017 , Volume 11 , Issue 1 , pages: 57
  • Center for Quantitative Medicine and Department of Cell Biology, UConn Health, Farmington, CT, 06030, USA.
  • Iron is an essential element of most living organisms but is a dangerous substance when poorly liganded in solution. The hormone hepcidin regulates the export of iron from tissues to the plasma contributing to iron homeostasis and also restricting its availability to infectious agents. Disruption of iron regulation in mammals leads to disorders such as anemia and hemochromatosis, and contributes to the etiology of several other diseases such as cancer and neurodegenerative diseases. Here we test the hypothesis that hepcidin alone is able to regulate iron distribution in different dietary regimes in the mouse using a computational model of iron distribution calibrated with radioiron tracer data.A model was developed and calibrated to the data from adequate iron diet, which was able to simulate the iron distribution under a low iron diet. However simulation of high iron diet shows considerable deviations from the experimental data. Namely the model predicts more iron in red blood cells and less iron in the liver than what was observed in experiments.These results suggest that hepcidin alone is not sufficient to regulate iron homeostasis in high iron conditions and that other factors are important. The model was able to simulate anemia when hepcidin was increased but was unable to simulate hemochromatosis when hepcidin was suppressed, suggesting that in high iron conditions additional regulatory interactions are important.
Contributors
Krishna Kumar Tiwari

Metadata information

hasTaxon
Taxonomy Mus musculus
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
Curation status
Curated
Name Description Size Actions

Model files

Parmar2017_Deficient_Rich_tracer.xml SBML L2V4 representation of Parmar2017 - Mouse Iron Distribution - Deficient and rich iron diet (Tracer) 195.89 KB Preview | Download

Additional files

Parmar2017_Deficient_Rich_tracer.sedml SEDML file 1.19 KB Preview | Download
Parmar2017_Deficient_Rich_tracer.cps COPASI 4.24 (build196) file depicting literature figure 3 and 4. 293.47 KB Preview | Download
Fig4_all.png Figure 4 result images (reproduced) 123.75 KB Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: Mar 4, 2019 4:40:13 PM
  • Last Modified: Mar 4, 2019 4:40:13 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Mar 4, 2019 4:40:13 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000734
Curator's comment:
(added: 04 Mar 2019, 16:36:05, updated: 04 Mar 2019, 16:36:05)
Figure Reproduced: Figure 3 and 4. Uploaded image in curation section is figure 3 and image for figure 4 will be updated under additional file section. Simulation Protocol: simulated for 30 days post NTBI stimulation. Run need to be done as Tasks --> parameter estimation --> run. Model is reproduced and simulated using COPASI 2.64 (build196) and figures are created using libreoffice calc.