Parmar2019 - Iron Mouse PV3

  public model
Model Identifier
MODEL1805140003
Short description

Iron Mouse PV3

"A computational model to understand mouse iron physiology and diseases"

By Jignesh Parmar and Pedro Mendes

Base model

This is a dynamic model of iron distribution in mice, covering seven compartments: plasma, bone marrow, red blood cells (RBC), spleen, duodenum, liver, and the rest of the body . This is mostly a physiological model with regulation by hepcidin and erythropoietin, including only a minimal amount of molecular details.

This version of the model does not include the radioactive-labelled tracer iron species that were used for parameter estimation (that is included in a separate file). This model has all parameter values already set to the best estimates obtained with the model with radioactive tracer. This model is useful to study the steady state properties of the system and as a basis for various types of simulation.

Model validation was carried out with other model files that were derived from this one and where certain parameters were altered or new interventions added.

Format
SBML (L2V4)
Related Publication
  • A computational model to understand mouse iron physiology and disease.
  • Jignesh H. Parmar, Mendes P
  • PLoS computational biology , 1/ 2019 , Volume 15 , Issue 1 , pages: e1006680 , PubMed ID: 30608934
  • Center for Quantitative Medicine and Department of Cell Biology, University of Connecticut School of Medicine, Farmington, Connecticut, United States of America.
  • It is well known that iron is an essential element for life but is toxic when in excess or in certain forms. Accordingly there are many diseases that result directly from either lack or excess of iron. Yet many molecular and physiological aspects of iron regulation have only been discovered recently and others are still elusive. There is still no good quantitative and dynamic description of iron absorption, distribution, storage and mobilization that agrees with the wide array of phenotypes presented in several iron-related diseases. The present work addresses this issue by developing a mathematical model of iron distribution in mice calibrated with ferrokinetic data and subsequently validated against data from mouse models of iron disorders, such as hemochromatosis, β-thalassemia, atransferrinemia and anemia of inflammation. To adequately fit the ferrokinetic data required inclusion of the following mechanisms: a) transferrin-mediated iron delivery to tissues, b) induction of hepcidin by transferrin-bound iron, c) ferroportin-dependent iron export regulated by hepcidin, d) erythropoietin regulation of erythropoiesis, and e) liver uptake of NTBI. The utility of the model to simulate disease interventions was demonstrated by using it to investigate the outcome of different schedules of transferrin treatment in β-thalassemia.
Contributors
Submitter of the first revision: Pedro Mendes
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Pedro Mendes, Krishna Kumar Tiwari

Metadata information

is
Gene Ontology iron ion homeostasis
Taxonomy Mus musculus
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Non-curated


Tags

Connected external resources

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Model files

IronMousePV3.xml SBML L2V4 representation of Iron Mouse PV3 154.85 KB Preview | Download

Additional files

IronMousePV3.cps Parmar2018 - IronMouse PV3 - base model, COPASI format 298.48 KB Preview | Download

  • Model originally submitted by : Pedro Mendes
  • Submitted: Jan 7, 2019 2:56:07 PM
  • Last Modified: Sep 16, 2022 11:42:00 AM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Sep 16, 2022 11:42:00 AM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Updated Publication details
  • Version: 3 public model Download this version
    • Submitted on: Jan 7, 2019 2:56:07 PM
    • Submitted by: Pedro Mendes
    • With comment: This model has been published and can now be made public (I cannot see where in the interface I could change it to public!)

(*) 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.