Journal article
Iron uptake from plasma transferrin by a transferrin receptor 2 mutant mouse model of haemochromatosis
Journal of Hepatology, Vol.52(3), pp.425-431
2010
Abstract
Background & Aims
Hereditary haemochromatosis type 3 is caused by mutations in transferrin receptor (TFR) 2. TFR2 has been shown to mediate iron transport in vitro and regulate iron homeostasis. The aim of this study was to determine the role of Tfr2 in iron transport in vivo using a Tfr2 mutant mouse.
Methods
Tfr2 mutant and wild-type mice were injected intravenously with 59Fe-transferrin and tissue 59Fe uptake was measured. Tfr1, Tfr2 and ferroportin expression was measured by real-time PCR and Western blot. Cellular localisation of ferroportin was determined by immunohistochemistry.
Results
Transferrin-bound iron uptake by the liver and spleen in Tfr2 mutant mice was reduced by 20% and 65%, respectively, whilst duodenal and renal uptake was unchanged compared with iron-loaded wild-type mice. In Tfr2 mutant mice, liver Tfr2 protein was absent, whilst ferroportin protein was increased in non-parenchymal cells and there was a low level of expression in hepatocytes. Tfr1 expression was unchanged compared with iron-loaded wild-type mice. Splenic Tfr2 protein expression was absent whilst Tfr1 and ferroportin protein expression was increased in Tfr2 mutant mice compared with iron-loaded wild-type mice.
Conclusions
A small reduction in hepatic transferrin-bound iron uptake in Tfr2 mutant mice suggests that Tfr2 plays a minor role in liver iron transport and its primary role is to regulate iron metabolism. Increased ferroportin expression due to decreased hepcidin mRNA levels is likely to be responsible for impaired splenic iron uptake in Tfr2 mutant mice.
Details
- Title
- Iron uptake from plasma transferrin by a transferrin receptor 2 mutant mouse model of haemochromatosis
- Authors/Creators
- A.C.G. Chua (Author/Creator)R.D. Delima (Author/Creator)E.H. Morgan (Author/Creator)C.E. Herbison (Author/Creator)J.E.E. Tirnitz-Parker (Author/Creator)R.M. Graham (Author/Creator)R.E. Fleming (Author/Creator)R.S. Britton (Author/Creator)B.R. Bacon (Author/Creator)J.K. Olynyk (Author/Creator)D. Trinder (Author/Creator)
- Publication Details
- Journal of Hepatology, Vol.52(3), pp.425-431
- Publisher
- Elsevier
- Identifiers
- 991005541206207891
- Copyright
- 2009 European Association for the Study of the Liver
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.184 Physiology & Metals
- 1.184.573 Iron Metabolism
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine