Barker J E, Pierce J E, Kefauver B C, Nienhuis A W
Proc Natl Acad Sci U S A. 1977 Nov;74(11):5078-82. doi: 10.1073/pnas.74.11.5078.
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.
在纯合βA珠蛋白链的绵羊中，出生前不久，HbF（α2γ2）的合成被HbA（α2βA2）的合成所取代，而HbC（α2βC2）在新生儿期短暂产生。我们通过在妊娠中期胎儿骨髓或肝脏的血浆凝块培养物中，在高促红细胞生成素浓度下生成红系集落，实现了从HbF到HbC的转换。此外，在从βA和βB基因杂合动物的细胞生长的集落中，高促红细胞生成素浓度似乎特异性地激活了βC基因，而不是βA或βB珠蛋白基因。以周期性出血或子宫内注射促红细胞生成素形式的造血应激，直到出生前不久才刺激胎儿绵羊体内HbC（α2βC2）的产生，而且仅在六只动物中的两只中出现。因此，除促红细胞生成素外的其他因素可能会影响胎儿绵羊体内βC珠蛋白合成的潜力。
