Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts

• Published in: Blood Vol. 98; no. 12; pp. 3261 - 3273
• Main Authors: Socolovsky, Merav, Nam, Hyung-song, Fleming, Mark D., Haase, Volker H., Brugnara, Carlo, Lodish, Harvey F.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.2001; The Americain Society of Hematology
• Subjects: Anemia - genetics; Anemias. Hemoglobinopathies; Animals; Apoptosis; bcl-X Protein; Biological and medical sciences; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; Diseases of red blood cells; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Erythroblasts - chemistry; Erythroblasts - pathology; Erythrocyte Count; Erythroid Precursor Cells - pathology; Erythropoiesis - genetics; Erythropoietin - physiology; Fetal Diseases - genetics; Fundamental and applied biological sciences. Psychology; Genotype; Hematocrit; Hematologic and hematopoietic diseases; Medical sciences; Mice; Mice, Inbred C57BL; Milk Proteins; Molecular and cellular biology; Polymerase Chain Reaction; Proto-Oncogene Proteins c-bcl-2 - analysis; Receptors, Erythropoietin - physiology; Spleen - chemistry; Spleen - pathology; STAT5 Transcription Factor; Stress, Physiological - physiopathology; Trans-Activators - deficiency; Trans-Activators - genetics; Trans-Activators - physiology; Erythropoiesis; Animal model; Ineffective erythropoiesis; Erythropoietin; Anemia; Rodentia; Glycoprotein hormone; Cell differentiation; Stress; Erythroblast; Signal transduction; Vertebrata; Mammalia; Mouse; Transcription factor STAT5; Hematopoiesis; Animal; Apoptosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.12.3261

Erythropoietin (Epo) controls red cell production in the basal state and during stress. Epo binding to its receptor, EpoR, on erythroid progenitors leads to rapid activation of the transcription factor Stat5. Previously, fetal anemia and increased apoptosis of fetal liver erythroid progenitors were found in Stat5a−/−5b−/− mice. However, the role of Stat5 in adult erythropoiesis was not clear. The present study shows that some adult Stat5a−/−5b−/− mice have a near-normal hematocrit but are deficient in generating high erythropoietic rates in response to stress. Further, many adult Stat5a−/−5b−/− mice have persistent anemia despite a marked compensatory expansion in their erythropoietic tissue. Analysis of erythroblast maturation in Stat5a−/−5b−/− hematopoietic tissue shows a dramatic increase in early erythroblast numbers, but these fail to progress in differentiation. Decreased expression of bcl-xLand increased apoptosis in Stat5a−/−5b−/−early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.