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Iron metabolism and ineffective erythropoiesis in beta-thalassemia mouse models - PubMed

  • ️Mon Mar 28 2011

Iron metabolism and ineffective erythropoiesis in beta-thalassemia mouse models

Pedro Ramos et al. Ann N Y Acad Sci. 2010 Aug.

Abstract

beta-thalassemia is a disease associated with decreased beta-globin production leading to anemia, ineffective erythropoiesis, and iron overload. New mechanisms associated with modulation of erythropoiesis and iron metabolism have recently been discovered in thalassemic mice, improving our understanding of the pathophysiology of this disease. These discoveries have the potential to be translated into clinically-relevant therapeutic options to reduce ineffective erythropoiesis and iron overload. A new generation of therapies based on limiting ineffective erythropoiesis, iron absorption, and the correction of iron maldistribution could be on the way, possibly complementing and improving the current standard of patient care.

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Figures

Figure 1
Figure 1

Effect of Jak2 on ineffective erythropoiesis in β-thalassemia. (A) Erythroid populations in splenic cell suspensions measured by classical CD71 and ter119 co-staining showing a decreased percentage of double positive cells in the animals treated with Jak2 inhibitor (right panel) compared to those of placebo treated mice (left panel). (B) Decrease in spleen size caused by treatment with the Jak2 inhibitor.

Figure 2
Figure 2

Hepcidin mRNA expression in liver samples from thalassemic mice. Hepcidin mRNA expression in the liver of th3/+ mice at different ages as measured by qPCR, showing very low levels of hepcidin expression in the early stages of the disease (2m) and an increase of hepcidin levels at later stages (1 year). The abbreviations 2m, 5m, and 12m indicate 2-month-old, 5-month-old, and 12-month-old mice.

Figure 3
Figure 3

Depletion of macrophages using clodronate-containing liposomes. (A)Immunohistochemical staining of splenic sections from animals treated with PBS or clodronate-containing liposomes using the F4/80 antibody. (B) FACS analysis of cells from BM and spleen showing a reduction of F4/80 positive cells 48 hours after treatment with clodronate-containing liposomes.

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