The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse

Erythropoietin and its receptor are required for definitive erythropoiesis and maturation of erythroid progenitor cells. Mice lacking the erythropoiet in receptor exhibit severe anemia and die at about embryonic day 13.5. This phenotype can be rescued by the human erythropoietin receptor transgene. A nimals expressing only the human erythropoietin receptor survived through a dulthood with normal hematologic parameters and appeared to respond appropr iately to induced anemic stress. In addition to restoration of erythropoies is during development, the cardiac defect associated with embryos lacking t he erythropoietin receptor was corrected and the increased apoptosis in fet al liver, heart, and brain in the erythropoietin receptor null phenotype wa s markedly reduced. These studies indicate that no species barrier exists b etween mouse and human erythropoietin receptor and that the human erythropo ietin receptor transgene is able to provide specific expression in hematopo ietic and other selected tissues to rescue erythropoiesis and other organ d efects observed in the erythropoietin receptor null mouse. (C) 2001 by The American Society of Hematology.