The Relation between Erythropoiesis and Plasma Erythropoietin Levels in Normal and Genetically Anaemic Mice during Prolonged Hypoxia or after Whole-Body Irradiation

When normal mice (B6D2F₁, WBB6F₁- +/+ and WCB6F₁- +/+) are exposed to constant hypoxia, they respond with a steady increase of PCV for about 3 weeks. Plasma erythropoietin increases sharply for the first 1 or 2 days only, then falls to control levels, with occasional temporary increases through the next 30–40 days. Genetically anaemic mice (WBB6F₁-W/W^v and WCB6F₁-Sl/Sl^d) respond differently. The W/W mice show an increase of PCV, and Sl/Sl^d mice do not, but both respond with large increases of plasma erythropoietin levels which persist, except for some temporary falls, through 16–40 days. The response to hypoxia of chimeric W/W mice, their anaemia cured by implantation of +/+ marrow cells, resembles that of normal +/+ mice much more than that of anaemic W/W mice. Although normal WBB6F₁- +/+ mice recover after 200 R whole-body irradiation at rates similar to those of other normal mice, anaemic WBB6F₁-W/W mice show delayed onset of haemopoietic recovery in spite of significant production of erythropoietin. Exogenous erythropoietin injected into mice disappears more slowly from the plasma of anaemic W/W mice than from the plasma of normal +/+ mice, and erythropoietin which has been passed through WBB6F₁- +/+ normal mice is not thereby made as effective in anaemic W/W mice as it is in normal mice. These findings are consistent with the view that although both W/W and Sl/Sl^d anaemic mice can produce large amounts of erythropoietin over prolonged periods, W/W mice remain anaemic because of a genetic defect in RBC precursors, and Sl/Sl^d mice remain anaemic because of a genetic defect in some part of the internal environment in which the RBC must develop. WBB6F₁-W/W anaemic mice, when exposed to hypoxia, excrete erythropoietin in their urine. When these mice have their kidneys removed and they are exposed to hypoxia for a short time there is no significant production of erythropoietin. The suggestion is made that some genetically anaemic large domestic animals, if they could be found, might be useful and needed sources of erythropoietin.