Hematopoietic deletion of transferrin receptor 2 in mice leads to a block in erythroid differentiation during iron-deficient anemia
Rishi, Gautam, Secondes, Eriza S., Wallace, Daniel F., & Subramaniam, V. Nathan (2016) Hematopoietic deletion of transferrin receptor 2 in mice leads to a block in erythroid differentiation during iron-deficient anemia. American Journal of Hematology, 91(8), pp. 812-818.
Iron metabolism and erythropoiesis are inherently interlinked physiological processes. Regulation of iron metabolism is mediated by the iron-regulatory hormone hepcidin. Hepcidin limits the amount of iron released into the blood by binding to and causing the internalization of the iron exporter, ferroportin. A number of molecules and physiological stimuli, including erythropoiesis, are known to regulate hepcidin. An increase in erythropoietic demand decreases hepcidin, resulting in increased bioavailable iron in the blood. Transferrin receptor 2 (TFR2) is involved in the systemic regulation of iron metabolism. Patients and mice with mutations in TFR2 develop hemochromatosis due to inappropriate hepcidin levels relative to body iron. Recent studies from our laboratory and others have suggested an additional role for TFR2 in response to iron-restricted erythropoiesis. These studies used mouse models with perturbed systemic iron metabolism: anemic mice lacking matriptase-2 and TFR2, or bone marrow transplants from iron-loaded TFR2 null mice. We developed a novel transgenic mouse model which lacks TFR2 in the hematopoietic compartment, enabling the delineation of the role of TFR2 in erythroid development without interfering with its role in systemic iron metabolism. We show that in the absence of hematopoietic TFR2 immature polychromatic erythroblasts accumulate with a concordant reduction in the percentage of mature erythroid cells in the spleen and bone marrow of anemic mice. These results demonstrate that erythroid TFR2 is essential for an appropriate erythropoietic response in iron-deficient anemia. These findings may be of relevance in clinical situations in which an immediate and efficient erythropoietic response is required.
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|Item Type:||Journal Article|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
|Copyright Owner:||© 2016 Wiley Periodicals, Inc.|
|Deposited On:||12 Oct 2016 00:18|
|Last Modified:||20 Oct 2016 04:39|
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