Residual erythroid progenitors in W/W mice respond to erythropoietin in the absence of steel factor signals

Erythropoiesis is severely impaired in mice with inactivating mutations in the Steel factor (SF) gene (Sl/Sl mice) or in c-kit, in the SF receptor gen e (W/W mice), and in mice with null mutations in the genes for either eryth ropoietin (EPO) or the erythropoietin receptor (EPO-R). Previous studies in dicated that EPO is sufficient for colony development from colony-forming u nits-erythroid (CFU-E). However, recent studies have shown that there is a physical association between these 2 receptors and that c-kit can phosphory late EPO-R. To examine the role SF and EPO play in regulating erythropoiesi s, we examined the effect of SF and EPO on colony development from cells of the embryonic aorta-gonad-mesonephros (AGM) region, yolk sac, and liver of fetal wild-type and W/W mice. The maturation of CFU-E from these sites did not require the addition of SF to clonal cultures, whereas the efficient d evelopment of erythroid bursts required both EPO and SE The number of eryth roid colony-forming cells was reduced in both the AGM region and liver of f etal W/W mice. The residual CFU-E present in W/W mice were dependent on EPO and independent of SF. These results indicate that EPO/EPO-R call function to support colony formation in the absence of an SF signal. Int J Hematol. 2000;72:178-185. (C) 2000 The Japanese Society of Hematology.