Iron homeostasis in beta-thalassemic mice

Abstract

To explore the pathogenesis of nontransfusional iron overload in iron- loading anemia, we examined features of external iron exchange, internal iron kinetics, and tissue iron burden in adult mice with inherited gene-deletion beta-thalassemia. Mice homozygous for beta- thalassemia display moderate anemia, reticulocytosis, and shortened red cell survival, whereas heterozygous carriers appear hematologically normal. Quantitative iron determination revealed that iron content and concentration in liver, spleen, and kidney, but not heart, were far higher (P less than .01) in 15-to 35-week old homozygous thalassemic mice than in age-matched normal and heterozygous controls; of these tissues, iron content increased with age only in kidneys (P = .01) of homozygous affected mice. Although plasma iron levels were only minimally elevated in homozygotes, plasma iron turnover was threefold greater (P less than .001) than that seen in heterozygote controls. Nevertheless hyperabsorption of enteric radioiron, discernible among homozygous thalassemic mice as late as 6 to 8 weeks after birth, was not observed in older mice, additionally, thalassemic and control mice at 18 to 34 weeks showed comparable iron excretion after intravenous radioiron. We conclude that adult mice with beta-thalassemia regain balanced external iron exchange, despite substantial tissue iron excess and accelerated internal iron transit.

Iron injections in mice increase skeletal muscle iron content, induce oxidative stress and reduce exercise performance

“…The blood drawn was spun down and the plasma removed then frozen at −20°C. The plasma was analysed for iron content using a photometric method (Van Wyck et al 1987; Lecube et al 2006) by Veterinary Pathology Diagnostic Services, University of Sydney.…”

Resistance to infection in murine beta-thalassemia

“…The plasma iron concentration was measured by a coulometric method, using a Ferrochem II analyzer (Environmental Sciences Associates, Bedford, Mass.). Total iron-binding capacity was determined by a proprietary resin exchange method as previously described (32).…”

“…In homozygous mice, on the other hand, there is incomplete 1-minor globin compensation, and these animals develop anemia, shortened erythrocyte survival, and splenomegaly, characteristics similar to those of human ,B-thalassemia. In conjunction with these characteristics, mice homozygous for the 3-major globin gene deletion have a marked increase in the iron content of the liver, spleen, and bone marrow, and plasma iron turnover is threefold greater than in heterozygous mice (32).…”