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.

View at publisher


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.

Impact and interest:

0 citations in Scopus
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 99744
Item Type: Journal Article
Refereed: Yes
DOI: 10.1002/ajh.24417
ISSN: 0361-8609
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

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page