GENERATION OF COMMITTED ERYTHROID BFU-E AND CFU-E PROGENITORS DOES NOT REQUIRE ERYTHROPOIETIN OR THE ERYTHROPOIETIN RECEPTOR

Erythropoietin (EPO) is the principal growth factor regulating the pro duction of circulating erythrocytes. We introduced null mutations into both Epo and the EPO receptor (EpoR) gene. Both heterozygotes appeare d normal. Homozygous animals exhibited reduced primitive erythropoiesi s and died around embryonic day 13, owing to failure of definitive fet al liver erythropoiesis. Both types of mutations exhibited identical p henotypes, indicating that EPO and the EPOR are crucial for definitive erythropoiesis in vivo and that no other ligands or receptors can rep lace them. Committed erythroid BFU-E and CFU-E progenitors were presen t in both homozygous fetal livers. Thus, neither EPO nor the EPOR is r equired for erythroid lineage commitment or for the proliferation and differentiation of BFU-E to CFU-E progenitors. EPO and the EPOR are cr ucial in vivo for the proliferation and survival of CFU-E progenitors and their irreversible terminal differentiation.