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Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3.
Am J Physiol Gastrointest Liver Physiol. 2007 Jan; 292(1):G323-8.AJ

Abstract

Hereditary hemochromatosis type 3 is an iron (Fe)-overload disorder caused by mutations in transferrin receptor 2 (TfR2). TfR2 is expressed highly in the liver and regulates Fe metabolism. The aim of this study was to investigate duodenal Fe absorption and hepatic Fe uptake in a TfR2 (Y245X) mutant mouse model of hereditary hemochromatosis type 3. Duodenal Fe absorption and hepatic Fe uptake were measured in vivo by 59Fe-labeled ascorbate in TfR2 mutant mice, wild-type mice, and Fe-loaded wild-type mice (2% dietary carbonyl Fe). Gene expression was measured by real-time RT-PCR. Liver nonheme Fe concentration increased progressively with age in TfR2 mutant mice compared with wild-type mice. Fe absorption (both duodenal Fe uptake and transfer) was increased in TfR2 mutant mice compared with wild-type mice. Likewise, expression of genes participating in duodenal Fe uptake (Dcytb, DMT1) and transfer (ferroportin) were increased in TfR2 mutant mice. Nearly all of the absorbed Fe was taken up rapidly by the liver. Despite hepatic Fe loading, hepcidin expression was decreased in TfR2 mutant mice compared with wild-type mice. Even when compared with Fe-loaded wild-type mice, TfR2 mutant mice had increased Fe absorption, increased duodenal Fe transport gene expression, increased liver Fe uptake, and decreased liver hepcidin expression. In conclusion, despite systemic Fe loading, Fe absorption and liver Fe uptake were increased in TfR2 mutant mice in association with decreased expression of hepcidin. These findings support a model in which TfR2 is a sensor of Fe status and regulates duodenal Fe absorption and liver Fe uptake.

Authors+Show Affiliations

School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, PO Box 480, Fremantle, 6959, WA, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16935854

Citation

Drake, S F., et al. "Iron Absorption and Hepatic Iron Uptake Are Increased in a Transferrin Receptor 2 (Y245X) Mutant Mouse Model of Hemochromatosis Type 3." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 292, no. 1, 2007, pp. G323-8.
Drake SF, Morgan EH, Herbison CE, et al. Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3. Am J Physiol Gastrointest Liver Physiol. 2007;292(1):G323-8.
Drake, S. F., Morgan, E. H., Herbison, C. E., Delima, R., Graham, R. M., Chua, A. C., Leedman, P. J., Fleming, R. E., Bacon, B. R., Olynyk, J. K., & Trinder, D. (2007). Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3. American Journal of Physiology. Gastrointestinal and Liver Physiology, 292(1), G323-8.
Drake SF, et al. Iron Absorption and Hepatic Iron Uptake Are Increased in a Transferrin Receptor 2 (Y245X) Mutant Mouse Model of Hemochromatosis Type 3. Am J Physiol Gastrointest Liver Physiol. 2007;292(1):G323-8. PubMed PMID: 16935854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3. AU - Drake,S F, AU - Morgan,E H, AU - Herbison,C E, AU - Delima,R, AU - Graham,R M, AU - Chua,A C G, AU - Leedman,P J, AU - Fleming,R E, AU - Bacon,B R, AU - Olynyk,J K, AU - Trinder,D, Y1 - 2006/08/24/ PY - 2006/8/29/pubmed PY - 2007/3/23/medline PY - 2006/8/29/entrez SP - G323 EP - 8 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 292 IS - 1 N2 - Hereditary hemochromatosis type 3 is an iron (Fe)-overload disorder caused by mutations in transferrin receptor 2 (TfR2). TfR2 is expressed highly in the liver and regulates Fe metabolism. The aim of this study was to investigate duodenal Fe absorption and hepatic Fe uptake in a TfR2 (Y245X) mutant mouse model of hereditary hemochromatosis type 3. Duodenal Fe absorption and hepatic Fe uptake were measured in vivo by 59Fe-labeled ascorbate in TfR2 mutant mice, wild-type mice, and Fe-loaded wild-type mice (2% dietary carbonyl Fe). Gene expression was measured by real-time RT-PCR. Liver nonheme Fe concentration increased progressively with age in TfR2 mutant mice compared with wild-type mice. Fe absorption (both duodenal Fe uptake and transfer) was increased in TfR2 mutant mice compared with wild-type mice. Likewise, expression of genes participating in duodenal Fe uptake (Dcytb, DMT1) and transfer (ferroportin) were increased in TfR2 mutant mice. Nearly all of the absorbed Fe was taken up rapidly by the liver. Despite hepatic Fe loading, hepcidin expression was decreased in TfR2 mutant mice compared with wild-type mice. Even when compared with Fe-loaded wild-type mice, TfR2 mutant mice had increased Fe absorption, increased duodenal Fe transport gene expression, increased liver Fe uptake, and decreased liver hepcidin expression. In conclusion, despite systemic Fe loading, Fe absorption and liver Fe uptake were increased in TfR2 mutant mice in association with decreased expression of hepcidin. These findings support a model in which TfR2 is a sensor of Fe status and regulates duodenal Fe absorption and liver Fe uptake. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/16935854/Iron_absorption_and_hepatic_iron_uptake_are_increased_in_a_transferrin_receptor_2__Y245X__mutant_mouse_model_of_hemochromatosis_type_3_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00278.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -