Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.

Socolovsky M, Nam H, Fleming MD, Haase VH, Brugnara C, Lodish HF
Blood. 2001 98 (12): 3261-73

PMID: 11719363 · 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-x(L) and increased apoptosis in Stat5a(-/-)5b(-/-) early erythroblasts correlate with the degree of anemia. Hence, Stat5 controls a rate-determining step regulating early erythroblast survival.

MeSH Terms (25)

Anemia Animals Apoptosis bcl-X Protein Cell Differentiation Cells, Cultured DNA-Binding Proteins Erythroblasts Erythrocyte Count Erythroid Precursor Cells Erythropoiesis Erythropoietin Fetal Diseases Genotype Hematocrit Mice Mice, Inbred C57BL Milk Proteins Polymerase Chain Reaction Proto-Oncogene Proteins c-bcl-2 Receptors, Erythropoietin Spleen STAT5 Transcription Factor Stress, Physiological Trans-Activators

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