Erythropoietin receptor haploinsufficiency and in vivo interplay with granulocyte-macrophage colony-stimulating factor and interleukin 3.

Abstract:

:Erythropoietin (EPO) and its receptor (EPOR) are critical for definitive erythropoiesis, as mice lacking either gene product die during embryogenesis with severe anemia. Here we demonstrate that mice expressing just one functional allele of the EpoR have lower hematocrits and die more frequently than do wild-type littermates on anemia induction. Furthermore, EpoR(+/-) erythroid colony-forming unit (CFU-E) progenitors are reduced both in frequency and in responsiveness to EPO stimulation. To evaluate the interaction between EPO and granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin 3 (IL-3), GM-CSF(-/-) or IL-3(-/-) mice were interbred with EpoR(+/)(-) mice. Deletion of either GM-CSF or IL-3 also leads to reduction in CFU-E numbers and hematocrits but does not significantly alter steady-state erythroid burst-forming unit numbers. These results suggest EpoR haploinsufficiency and promotion of in vivo erythropoiesis by GM-CSF and IL-3.

journal_name

Blood

journal_title

Blood

authors

Jegalian AG,Acurio A,Dranoff G,Wu H

doi

10.1182/blood.v99.7.2603

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

2603-5

issue

7

eissn

0006-4971

issn

1528-0020

journal_volume

99

pub_type

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