The hematopoietic stem cell concentrations in tissues of homozygous beta-thalassemic and non-thalassemic fetuses and neonates were compared by using the spleen colony-forming units (CFU-S) assay. The relative quantities of embryonic and adult hemoglobins were also determined for fetuses. Beta-thalassemic fetuses had a reduced incidence of CFU-S in the liver throughout gestation, but after birth the beta-thalassemic neonates maintained a greater number of CFU-S in the liver for an extended period. The incidence of CFU-S in the bone marrow was not different for the two groups. The beta-thalassemic mice exhibited a significant expansion of CFU-S in the spleen beyond 11 days after birth. The switch from the synthesis of primarily embryonic to primarily adult hemoglobins in circulating erythrocytes in beta-thalassemic fetuses appeared later than the switch in normal fetuses. These observations establish that the developmental timing and expansion of hematopoiesis are perturbed in beta-thalassemic mice.

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