Barker J E, Last J A, Adams S L, Nienhuis A W, Anderson W F
Proc Natl Acad Sci U S A. 1973 Jun;70(6):1739-43. doi: 10.1073/pnas.70.6.1739.
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.
绵羊和山羊体内发生的由贫血诱导的从血红蛋白A(α₂β₂(A))合成向血红蛋白C(α₂β₂(C))合成的转变,已在山羊骨髓细胞的组织培养中重现。在促红细胞生成素存在的情况下培养山羊骨髓原代培养物,48 - 72小时后会出现可检测量的β(C)珠蛋白,同时β(A)珠蛋白减少。在促红细胞生成素处理的培养物中,一群早幼红细胞以及活跃的血红素和珠蛋白合成至少维持3天,但在缺乏促红细胞生成素的培养物中则不然。这些发现证明了(i)体外维持骨髓中对促红细胞生成素反应性细胞,以及(ii)体外从由一个基因编码的珠蛋白链合成转变为由不同的非等位基因编码的珠蛋白链合成。骨髓培养可能是研究促红细胞生成素作用机制以及体外研究特定基因激活(和失活)的有用模型系统。