Belgrade
Rats Display Liver Iron Loading
Patients
with mutations in divalent metal transporter-1 (DMT1), an intestinal nonheme
iron transporter, suffer from microcytic anemia and hepatic iron loading. DMT1
is also mutated in Belgrade rats, an animal model with a thalassemic-like
disorder of microcytic anemia with hyperferrinemia. However, aspects of hepatic
iron loading in this genetic model are not well characterized. To more fully
define the Belgrade rat’s iron status, we compared the characteristics of homozygous
(b/b) and heterozygous (b/1) rats fed an iron-supplemented diet for 3 wk
postweaning. Dietary supplementation with ferrous iron improved the anemia of
b/brats insofar as hematocrits increased from 0.13 (21-d–old) to 0.31
(42-d–old). However, hematocrits remained significantly lower than those of
age-matchedb/1rats (0.36 and 0.41 in 21- and 42-d–old heterozygotes,
respectively,P,0.05). Wright’s staining ofb/bred cells confirmed the
hypochromic microcytic nature of Belgrade rats’ anemia. The liver iron
concentration of 42-d–oldb/brats was greater than in age-matchedb/1rats (5.97
vs. 2.24mmol/g,P,0.05). Whereas Perls’ Prussian blue iron staining was evident
in both periportal and centrilobular regions in 42-d–old b/bliver sections, no
staining was observed in age-matched b/1tissue sections. Quantitative real-time
PCR analysis showed that expression of liver hepcidin mRNA in 42-d–oldb/brats
was 3-fold greater than age-matchedb/1rats. These results indicate that,
similar to human patients with DMT1 mutations, Belgrade rats also display
hepatic iron loading. Our data suggest this condition arises from ineffective
erythropoiesis. J. Nutr. 136: 3010–3014, 2006.
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