Dataset Information

Parmar2019 - Iron Mouse PV3 - tracer

ABSTRACT: Iron Mouse PV3 "A computational model to understand mouse iron physiology and diseases" By Jignesh Parmar and Pedro Mendes Parameter estimation using radioactive tracer data 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 includes normal iron species and radioactive-labelled tracer iron species. It was used specifically for parameter estimation using the data from Schümann et al. 2007 (see also Lopes et al. 2010 and Parmar et al. 2017) from three experiments of mice fed adequate, iron-deficient, and iron-rich diets. Mice in all three dietary regimes were injected with a radiactive tracer and its distribution measured along time. The model parameters were adjusted in order to minimize the distance of the model to the data of all three experiements simultaneously. Model validation was carried out with another version of this model where the radioactive species are ommited but all parameters remain with the values determined here (see accompanying model). The model is able to match the phenotype of several iron-related diseases.

SUBMITTER: Pedro Mendes

PROVIDER: MODEL1805140002 | BioModels | 2022-09-16

REPOSITORIES: BioModels

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Publications

A computational model to understand mouse iron physiology and disease.

Parmar Jignesh H JH Mendes Pedro P

PLoS computational biology 20190104 1

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 pres ...[more]

PMID: 30608934

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Project description:This a model from the article: Systems analysis of iron metabolism: the network of iron pools and fluxes Tiago JS Lopes, Tatyana Luganskaja, Maja Vujic-Spasic, Matthias W Hentze, Martina U Muckenthaler, Klaus Schumann and Jens G Reich BMC Systems Biology2010, Aug 13;4(1):112. 20704761, Abstract: Background Every cell of the mammalian organism needs iron in numerous oxido-reductive processes as well as for transport and storage of oxygen. The versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in the cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, excretion and intra-body distribution. Intracellular regulation in different cell types is intertwined with a global hormonal signaling structure. Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole. Results Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on ferrokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, iron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartment) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearance rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distribution into different organs, of tracer-accessible pool sizes and of residence times of iron in the different compartments in response to three states of iron-repletion induced by the dietary regime. Conclusions This mathematical model presents a comprehensive physiological picture of mice under three different diets with varying iron contents. The quantitative results reflect systemic properties of iron metabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron storage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place. This model corresponds to the Iron Loaded condition - Mice This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Project description:This a model from the article: Systems analysis of iron metabolism: the network of iron pools and fluxes Tiago JS Lopes, Tatyana Luganskaja, Maja Vujic-Spasic, Matthias W Hentze, Martina U Muckenthaler, K laus Schumann and Jens G Reich BMC Systems Biology2010, Aug 13;4(1):112. 20704761, Abstract: Background Every cell of the mammalian organism needs iron in numerous oxido-reductive processes as well as fo r transport and storage of oxygen. The versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in t he cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, ex cretion and intra-body distribution. Intracellular regulation in different cell types is intertwine d with a global hormonal signaling structure. Iron deficiency as well as excess of iron are frequen t and serious human disorders. They can affect every cell, but also the organism as a whole. Results Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on f errokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, i ron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartme nt) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearanc e rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distr ibution into different organs, of tracer-accessible pool sizes and of residence times of iron in th e different compartments in response to three states of iron-repletion induced by the dietary regim e. Conclusions This mathematical model presents a comprehensive physiological picture of mice under three differen t diets with varying iron contents. The quantitative results reflect systemic properties of iron me tabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron s torage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place. This model corresponds to the Iron Deficient condition - Mice This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Project description:This a model from the article: Systems analysis of iron metabolism: the network of iron pools and fluxes Tiago JS Lopes, Tatyana Luganskaja, Maja Vujic-Spasic, Matthias W Hentze, Martina U Muckenthaler, K laus Schumann and Jens G Reich BMC Systems Biology2010, Aug 13;4(1):112. 20704761, Abstract: Background Every cell of the mammalian organism needs iron in numerous oxido-reductive processes as well as fo r transport and storage of oxygen. The versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in t he cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, ex cretion and intra-body distribution. Intracellular regulation in different cell types is intertwine d with a global hormonal signaling structure. Iron deficiency as well as excess of iron are frequen t and serious human disorders. They can affect every cell, but also the organism as a whole. Results Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on f errokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, i ron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartme nt) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearanc e rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distr ibution into different organs, of tracer-accessible pool sizes and of residence times of iron in th e different compartments in response to three states of iron-repletion induced by the dietary regim e. Conclusions This mathematical model presents a comprehensive physiological picture of mice under three differen t diets with varying iron contents. The quantitative results reflect systemic properties of iron me tabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron s torage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place. This model corresponds to the Iron Adequate condition - Mice This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Dataset Information

Parmar2019 - Iron Mouse PV3 - tracer

Publications

A computational model to understand mouse iron physiology and disease.

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