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The anemia-induced switch from hemoglobin A (alpha(2)beta(2) (A)) to hemoglobin C (alpha(2)beta(2) (C)) synthesis occurring in vivo in sheep and goats has been reproduced in tissue culture of goat bone-marrow cells. Cultivation of primary cultures of goat bone marrow in the presence of erythropoietin results in the appearance of detectable amounts of beta(C) globin after 48-72 hr, as well as in a decrease in beta(A) globin. A population of proerythroblasts, as well as active heme and globin synthesis, are maintained for at least 3 days in erythropoietin-treated, but not in erythropoietin-deficient, cultures. These findings demonstrate (i) maintenance of erythropoietin-responsive cells from bone marrow in vitro, and (ii) switching in vitro from the synthesis of a globin chain coded by one gene to that coded by a different, nonallelic gene. Bone-marrow culture might be a useful model system for study of the mechanism of action of erythropoietin and for study of the activation (and inactivation) of specific genes in vitro.

Hemogloblin Switching in Sheep and Goats: Erythropoietin-Dependent Synthesis of Hemoglobin C in Goat Bone-Marrow Cultures