Severe hypochromic microcytic anemia caused by a congenital defect of the iron transport pathway in erythroid cells

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Abstract
Recently, it has been shown that the microcytic anemia (mk) mouse1 and the Belgrade rat2 carry the same missense mutation (G185R) in DMT1. Homozygous animals demonstrate diminished intestinal iron absorption and a severe deficit in erythroid iron use. The reduced rate of heme synthesis in reticulocytes from Belgrade rats can be corrected by the iron chelate salicylaldehyde isonicotinoyl hydrazone saturated with iron (Fe-SIH),3 which is known to bypass the TfR/DMT1 cycle of iron transport.4 These results indicate that DMT1 plays a crucial role in erythroid iron uptake, since the most prominent consequence of impaired DMT1 function is disturbed erythropoiesis. Even though the residual activity of this transporter in affected rodents allows the animals to remain viable, it is not sufficient to ensure appropriate rate of iron supply and subsequent heme synthesis in the erythroid cells.