Wu H, Liu X, Jaenisch R, Lodish H F
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Cell. 1995 Oct 6;83(1):59-67. doi: 10.1016/0092-8674(95)90234-1.
Erythropoietin (EPO) is the principal growth factor regulating the production of circulating erythrocytes. We introduced null mutations into both Epo and the EPO receptor (EpoR) gene. Both heterozygotes appeared normal. Homozygous animals exhibited reduced primitive erythropoiesis and died around embryonic day 13, owing to failure of definitive fetal liver erythropoiesis. Both types of mutations exhibited identical phenotypes, indicating that EPO and the EPOR are crucial for definitive erythropoiesis in vivo and that no other ligands or receptors can replace them. Committed erythroid BFU-E and CFU-E progenitors were present in both homozygous fetal livers. Thus, neither EPO nor the EPOR is required for erythroid lineage commitment or for the proliferation and differentiation of BFU-E to CFU-E progenitors. EPO and the EPOR are crucial in vivo for the proliferation and survival of CFU-E progenitors and their irreversible terminal differentiation.
促红细胞生成素（EPO）是调节循环红细胞生成的主要生长因子。我们在Epo和促红细胞生成素受体（EpoR）基因中都引入了无效突变。两种杂合子看起来都正常。纯合动物表现出原始红细胞生成减少，并在胚胎第13天左右死亡，原因是确定性胎儿肝脏红细胞生成失败。两种类型的突变都表现出相同的表型，表明EPO和EPOR对体内确定性红细胞生成至关重要，并且没有其他配体或受体可以替代它们。纯合胎儿肝脏中都存在定向红系爆式形成单位（BFU-E）和集落形成单位-红细胞（CFU-E）祖细胞。因此，EPO和EPOR对于红系谱系定向或BFU-E向CFU-E祖细胞的增殖和分化都不是必需的。EPO和EPOR在体内对于CFU-E祖细胞的增殖和存活及其不可逆的终末分化至关重要。
