Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction

Cell. 1999 Jul 23;98(2):181-91. doi: 10.1016/s0092-8674(00)81013-2.


The erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a-/-5b-/- mice have normal steady-state hematocrit. Here we show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a-/-5b-/- embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X(L) in erythroid cells through direct binding to the Bcl-X promoter.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anemia / genetics*
  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Cell Line
  • Consensus Sequence
  • DNA-Binding Proteins / genetics*
  • Enhancer Elements, Genetic / physiology
  • Erythrocytes / cytology
  • Erythrocytes / drug effects
  • Erythropoietin / pharmacology
  • Gene Expression Regulation, Developmental
  • Genes, Immediate-Early / physiology
  • Hematocrit
  • Hematopoietic Stem Cells / cytology*
  • Mice
  • Mice, Knockout
  • Milk Proteins*
  • Promoter Regions, Genetic / physiology
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction / genetics
  • Trans-Activators / genetics*
  • Transcription, Genetic / physiology
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • DNA-Binding Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Trans-Activators
  • bcl-X Protein
  • Erythropoietin