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 gene (W/W mice), and in mice with null mutations in the genes for either erythropoietin (EPO) or the erythropoietin receptor (EPO-R). Previous studies indicated that EPO is sufficient for colony development from colony-forming units-erythroid (CFU-E). However, recent studies have shown that there is a physical association between these 2 receptors and that c-kit can phosphorylate EPO-R. To examine the role SF and EPO play in regulating erythropoiesis, 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 development of erythroid bursts required both EPO and SE The number of erythroid colony-forming cells was reduced in both the AGM region and liver of fetal 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 can function to support colony formation in the absence of an SF signal.
Pharr
P N
PN
Department of Veterans Affairs, Ralph H. Johnson Medical Center, Charleston, South Carolina, USA. pharrpn@musc.edu
Hofbauer
A
A
Worthington
R E
RE
Longmore
G D
GD
D000818:Animals; D018929:Cell Culture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
D019089:Stem Cell Factor; D004921:Erythropoietin; D019009:Proto-Oncogene Proteins c-kit