Hemoglobin switching in sheep and goats: erythropoietin dependent synthesis of hemoglobin C in goat bone marrow cultures

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 narrow 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 maintenance of erythropoietin responsive cells from bone marrow in vitro, and 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.