Faculty Research 1980 - 1989

The hematopoietic stem cells of alpha-thalassemic mice.

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Bone-Marrow: cy, tr, Cell-Differentiation: re, Colony-Forming-Units-Assay, Erythrocytes: cy, Female, Hematopoietic-Stem-Cells: cl, cy, Hemoglobins: ge, Male, Mice, Mice-Inbred-C57BL: bl, ge, Phenotype, Radiation-Chimera, Spleen: cy, SUPPORT-U-S-GOVT-P-H-S, Thalassemia: bl, fg, pa

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Blood. 1985 Sep; 66(3):595-601.




The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.

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