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Abstract
Despite the importance of blood platelets in health and disease, the mechanisms regulating
their formation within megakaryocytes are unknown. We generated mice lacking the hematopoietic
subunit (p45) of the heterodimeric erythroid transcription factor NF-E2. Unexpectedly,
NF-E2-/- mice lack circulating platelets and die of hemorrhage; their megakaryocytes
show no cytoplasmic platelet formation. Though platelets are absent, serum levels
of the growth factor thrombopoietin/MGDF are not elevated above controls. Nonetheless,
NF-E2-/- megakaryocytes proliferate in vivo in response to thrombopoietin administration.
Thus, as an essential factor for megakaryocyte maturation and platelet production,
NF-E2 must regulate critical target genes independent of the action of thrombopoietin.
These findings provide insight into the genetic analysis of megakaryocyte maturation
and thrombopoiesis.