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BioMed Research International
Volume 2017, Article ID 2408941, 12 pages
https://doi.org/10.1155/2017/2408941
Research Article

Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis

1Department of Clinical and Biological Sciences, AOU San Luigi Gonzaga, University of Torino, Orbassano, Torino, Italy
2Department of Veterinary Sciences, University of Torino, Grugliasco, Torino, Italy

Correspondence should be addressed to A. Roetto; ti.otinu@otteor.allenotna

Received 7 September 2016; Revised 1 March 2017; Accepted 4 April 2017; Published 2 May 2017

Academic Editor: Francesco Onida

Copyright © 2017 R. M. Pellegrino et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Type 3 haemochromatosis (HFE3) is a rare genetic iron overload disease which ultimately lead to compromised organs functioning. HFE3 is caused by mutations in transferrin receptor 2 (TFR2) gene that codes for two main isoforms (Tfr2α and Tfr2β). Tfr2α is one of the hepatic regulators of iron inhibitor hepcidin. Tfr2β is an intracellular isoform of the protein involved in the regulation of iron levels in reticuloendothelial cells. It has been recently demonstrated that Tfr2 is also involved in erythropoiesis. This study aims to further investigate Tfr2 erythropoietic role by evaluating the erythropoiesis of two Tfr2 murine models wherein either one or both of Tfr2 isoforms have been selectively silenced (Tfr2 KI and Tfr2 KO). The evaluations were performed in bone marrow and spleen, in 14 days’ and 10 weeks’ old mice, to assess erythropoiesis in young versus adult animals. The lack of Tfr2α leads to macrocytosis with low reticulocyte number and increased hemoglobin values, together with an anticipation of adult BM erythropoiesis and an increased splenic erythropoiesis. On the other hand, lack of Tfr2β (Tfr2 KI mice) causes an increased and immature splenic erythropoiesis. Taken together, these data confirm the role of Tfr2α in modulation of erythropoiesis and of Tfr2β in favoring iron availability for erythropoiesis.