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Synthesis of HbF (alpha2gamma2) is replaced by synthesis of Hb A (alpha2betaA2) shortly before birth in sheep homozygous for the betaA globin chain whereas Hb C (alpha2betaC2) is produced transiently during the neonatal period. We have obtained a Hb F-to-Hb C switch by generating erythroid colonies at high erythropoietin concentration in plasma clot cultures of mid-gestation fetal bone marrow or liver. Furthermore, high erythropoietin concentration appeared specifically to activate the gene for betaC and not those for betaA or betaB globin in colonies grown from cells of an animal heterozygous for the betaA and betaB genes. Erythropoietic stress in the form of periodic bleeding or erythropoietin injection in utero did not stimulate production of Hb C (alpha2betaC2) in fetal sheep until shortly before birth, and then only in two of six animals. Thus, factors other than erythropoietin may influence the potential for betaC globin synthesis in vivo in fetal sheep.

Hemoglobin switching in sheep and goats: induction of hemoglobin C synthesis in cultures of sheep fetal erythroid cells.