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 erythropoietin receptor exhibit severe anemia and die at about embryonic day 13.5. This phenotype can be rescued by the human erythropoietin receptor transgene. Animals expressing only the human erythropoietin receptor survived through adulthood with normal hematologic parameters and appeared to respond appropriately to induced anemic stress. In addition to restoration of erythropoiesis during development, the cardiac defect associated with embryos lacking the erythropoietin receptor was corrected and the increased apoptosis in fetal liver, heart, and brain in the erythropoietin receptor null phenotype was markedly reduced. These studies indicate that no species barrier exists between mouse and human erythropoietin receptor and that the human erythropoietin receptor transgene is able to provide specific expression in hematopoietic and other selected tissues to rescue erythropoiesis and other organ defects observed in the erythropoietin receptor null mouse.
Yu
X
X
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD 20892-1822, USA.
Lin
C S
CS
Costantini
F
F
Noguchi
C T
CT
D000740:Anemia / Q000139:chemically induced / Q000235:genetics / Q000628:therapy; D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D003114:Colony-Forming Units Assay; D003433:Crosses, Genetic; D004920:Erythropoiesis / Q000235:genetics*; D004921:Erythropoietin / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D017467:Receptors, Erythropoietin / Q000172:deficiency* / Q000235:genetics*; D013154:Spleen / Q000378:metabolism
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin