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, 98 (2), 181-91

Fetal Anemia and Apoptosis of Red Cell Progenitors in Stat5a-/-5b-/- Mice: A Direct Role for Stat5 in Bcl-X(L) Induction

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Fetal Anemia and Apoptosis of Red Cell Progenitors in Stat5a-/-5b-/- Mice: A Direct Role for Stat5 in Bcl-X(L) Induction

M Socolovsky et al. Cell.

Abstract

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.

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