Abstract

Type 3 haemochromatosis is a rare inherited iron excess condition that results in organ dysfunction. Mutations in the transferrin receptor 2 gene, which codes for two major isoforms, cause HFE3. Tfr2 is a hepatic regulator of the iron inhibitor hepcidin. Tfr2 is an intracellular isoform of the protein that controls iron levels in reticuloendothelial cells. Tfr2 is also important in erythropoiesis, as recently revealed. Tfr2 deficiency causes macrocytosis with reduced reticulocyte number and higher haemoglobin levels, as well as an increase in adult BM erythropoiesis and splenic erythropoiesis. Tfr2 deficiency, on the other hand, results in enhanced and immature splenic erythropoiesis. Taken together, our findings support the involvement of Tfr2 in erythropoiesis regulation and Tfr2 in promoting iron availability for erythropoiesis.