Mouse Iron Distribution - Deficient iron diet (No Tracer)

  public model
Model Identifier
BIOMD0000000737
Short description

Mouse Iron Distribution Dynamics

Dynamic model of iron distribution in mice. This model includes only normal iron with the parameters that fit the data from Lopes et al. 2010 for mice fed a deficient iron diet.

This model does not include the radioiron tracer species. It is appropriate to study the properties in conditions where no tracers are used (for example for steady state analysis).
Format
SBML (L2V4)
Related Publication
  • Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient.
  • Parmar JH, Davis G, Shevchuk H, Mendes P
  • BMC systems biology , 5/ 2017 , Volume 11 , Issue 1 , pages: 57 , PubMed ID: 28521769
  • 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
Submitter of the first revision: Pedro Mendes
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Pedro Mendes, Krishna Kumar Tiwari

Metadata information

hasTaxon (1 statement)
Taxonomy Mus musculus

is (3 statements)
Gene Ontology iron ion homeostasis
BioModels Database MODEL1605030004
BioModels Database BIOMD0000000737

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
Parmar2017_Deficient_NoTracer.xml SBML L2V4 representation of Parmar2017 - Mouse Iron Distribution - Deficient iron diet (No Tracer) 108.40 KB Preview | Download

Additional files
MODEL1605030004-biopax2.owl Auto-generated BioPAX (Level 2) 31.11 KB Preview | Download
MODEL1605030004-biopax3.owl Auto-generated BioPAX (Level 3) 52.00 KB Preview | Download
MODEL1605030004.m Auto-generated Octave file 13.62 KB Preview | Download
MODEL1605030004.png Auto-generated Reaction graph (PNG) 150.31 KB Preview | Download
MODEL1605030004.sci Auto-generated Scilab file 5.99 KB Preview | Download
MODEL1605030004.svg Auto-generated Reaction graph (SVG) 45.84 KB Preview | Download
MODEL1605030004.vcml Auto-generated VCML file 897.00 Bytes Preview | Download
MODEL1605030004.xpp Auto-generated XPP file 9.94 KB Preview | Download
MODEL1605030004_urn.xml Auto-generated SBML file with URNs 98.05 KB Preview | Download
Parmar2017_Deficient_NoTracer.cps COPASI 4.24 (build196) file depicting Deficient Table 3 results 163.66 KB Preview | Download
Parmar2017_Deficient_NoTracer.sedml SEDML file 13.79 KB Preview | Download

  • Model originally submitted by : Pedro Mendes
  • Submitted: May 3, 2016 8:49:32 PM
  • Last Modified: Mar 4, 2019 4:45:48 PM
Revisions
  • Version: 5 public model Download this version
    • Submitted on: Mar 4, 2019 4:45:48 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000737
  • Version: 2 public model Download this version
    • Submitted on: May 19, 2017 4:27:59 PM
    • Submitted by: Pedro Mendes
    • With comment: Current version of Parmar2017 - Mouse Iron Distribution - Deficient iron diet
  • Version: 1 public model Download this version
    • Submitted on: May 3, 2016 8:49:32 PM
    • Submitted by: Pedro Mendes
    • With comment: Original import of Mouse Iron Distribution - Deficient iron diet

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
FeRBC

iron cation 		0.0379799887571665 mol
Tf

Serotransferrin 		1.5821833083706E-5 mol
FeDuo

iron cation 		0.0117590568706314 mol
Hepcidin

Hepcidin 		2.30017456622937E-8 mol
Fe2Tf

Serotransferrin ; iron(3+) 		1.35248196757048E-5 mol
FeBM

iron cation 		0.00303783614844319 mol
FeLiver

iron cation 		0.00200010981212238 mol
NTBI

iron cation 		3.3311210465159E-8 mol
Reactions
Reactions Rate Parameters
FeBM => FeRBC kInRBC*FeBM*BoneMarrow kInRBC = 1.08447580176706
Fe2Tf => FeBM + Tf kInBM*Fe2Tf*Plasma kInBM = 15.7690636138556
Fe2Tf => FeDuo + Tf kInDuo*Fe2Tf*Plasma kInDuo = 0.0689984226081531
Hepcidin => Plasma*k1*Hepcidin k1=0.75616
Fe2Tf => FeLiver + Tf kInLiver*Fe2Tf*Plasma kInLiver = 2.97790545667672
Fe1Tf => FeLiver + Tf kInLiver*Fe1Tf*Plasma kInLiver = 2.97790545667672
=> Hepcidin Plasma*v v=8.54927E-9
FeSpleen => NTBI; Hepcidin VSpleenNTBI*Spleen*FeSpleen/((Km+FeSpleen)*(1+Hepcidin/Ki)) VSpleenNTBI = 1.342204923; Km = 0.0159421218669513; Ki = 1.0E-9
Curator's comment:
(added: 04 Mar 2019, 16:19:04, updated: 04 Mar 2019, 16:19:04)
Reproduced Figure: Reproduced the reported data of total iron mass reduce by 23 % (2.2 to 1.7 mg) and transferrin saturation from 47 to 37%. Simulation condition: Time for simulation: 100 days. Value of vDiet changed according to Deficient diet condition. Mode is reproduced and simulated using COPASI 4.24 (build 196). Figures are created using libreoffice calc.