Pharr P N, Hofbauer A, Worthington R E, Longmore G D
Department of Veterans Affairs, Ralph H. Johnson Medical Center, Charleston, South Carolina, USA.
Int J Hematol. 2000 Aug;72(2):178-85.
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.
在具有Steel因子（SF）基因失活突变的小鼠（Sl/Sl小鼠）、c-kit基因失活突变的小鼠、SF受体基因失活的小鼠（W/W小鼠）以及促红细胞生成素（EPO）或促红细胞生成素受体（EPO-R）基因无功能突变的小鼠中，红细胞生成严重受损。先前的研究表明，EPO足以支持红系集落形成单位（CFU-E）的集落发育。然而，最近的研究表明，这两种受体之间存在物理关联，并且c-kit可以使EPO-R磷酸化。为了研究SF和EPO在调节红细胞生成中的作用，我们检测了SF和EPO对野生型胎儿和W/W小鼠胚胎主动脉-性腺-中肾（AGM）区、卵黄囊和肝脏细胞集落发育的影响。来自这些部位的CFU-E成熟不需要在克隆培养中添加SF，而红系爆式集落的有效发育则需要EPO和SF。胎儿W/W小鼠的AGM区和肝脏中红系集落形成细胞的数量均减少。W/W小鼠中残留的CFU-E依赖于EPO且不依赖于SF。这些结果表明，在没有SF信号的情况下，EPO/EPO-R可以发挥支持集落形成的作用。
