Spontaneous Iron Overload in α-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 α-thalassemia. Mice heterozygous for a radiation-induced α-Hb gene deletion exhibit a mild hemo...

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Bibliographic Details
Published in:Blood 1984-07, Vol.64 (1), p.263-266
Main Authors: Wyck, David B. Van, Popp, Raymond A., Foxley, John, Witte, Marlys H., Witte, Charles L., Crosby, William H.
Format: Article
Language:English
Subjects:
Animals
Female
Intestinal Absorption
Iron - analysis
Kidney - analysis
Liver - analysis
Male
Mice
Mice, Mutant Strains
Myocardium - analysis
Rodent Diseases
Siderosis - etiology
Spleen - analysis
Spleen - pathology
Thalassemia - complications
Thalassemia - genetics
Thalassemia - veterinary
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Summary: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 α-thalassemia. Mice heterozygous for a radiation-induced α-Hb gene deletion exhibit a mild hemolytic anemia, like the human condition, with microcytosis, reticulocytosis, splenomegaly, and chemical evidence of defective α-chain synthesis. Quantitative iron determination showed that total iron content in spleen, liver, and kidney, but not heart or lung, of adult α-thalassemic mice was greater (P < .05) than that in unaffected littermates. Iron concentration was also increased in liver (P < .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 < .001), and heart (r = .46, P < .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, α-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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V64.1.263.263