Spontaneous iron overload in alpha-thalassemic mice.
Because clinical disorders of spontaneous iron overload have no experimental counterpart, we studied iron distribution (atomic absorption analysis) and intestinal absorption (59Fe) in mice with hereditary alpha-thalassemia. Mice heterozygous for a radiation-induced alpha-Hb gene deletion exhibit a mild hemolytic anemia, like the human condition, with microcytosis, reticulocytosis, splenomegaly, and chemical evidence of defective alpha-chain synthesis. Quantitative iron determination showed that total iron content in spleen, liver, and kidney, but not heart or lung, of adult alpha-thalassemic mice was greater (P less than .05) than that in unaffected littermates. Iron concentration was also increased in liver (P less than .001), spleen (P = .025), kidney (P = .058), and heart (P = .010); in general, the greater the iron concentration in liver, the greater that in spleen (r = .39, P = .009), kidney (r = .70, P less than .001), and heart (r = .46, P less than .001). In mice examined 8 months postoperatively, splenectomy, as compared to sham operation, significantly raised iron content in extrasplenic tissues, but did not affect total body iron. At 10-11 weeks of age, but no longer at 12-14 weeks, thalassemic mice showed higher rates of iron absorption than age-matched controls. Thus, alpha-thalassemic mice display an early occurring iron absorption defect, leading to a modest, sustained, nonprogressive iron overload, and thereby represent a valuable model for exploring disorders of iron homeostasis.
D000818:Animals; D005260:Female; D007408:Intestinal Absorption; D007501:Iron / Q000032:analysis; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000032:analysis; D012376:Rodent Diseases; D012806:Siderosis / Q000209:etiology*; D013154:Spleen / Q000032:analysis / Q000473:pathology; D013789:Thalassemia / Q000150:complications / Q000235:genetics / Q000662:veterinary*
D007501:Iron