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

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The anemia-induced switch from hemoglobin A (α2β2A) to hemoglobin C (α2β2C) 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 βC globin after 48-72 hr, as well as in a decrease in βA 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.

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