The role of transcription factor NF-E2 in megakaryocyte maturation and platelet production.
To determine the in vivo functions of the transcription factor NF-E2, we have disrupted the gene encoding its hematopoietic-specific p45 subunit in embryonic stem cells and generated knockout mice. These animals have a surprisingly mild erythroid cell abnormality but experience lethal hemorrhage as a result of profound thrombocytopenia. Impaired platelet formation is secondary to a cytoplasmic maturation arrest within megakaryocytes, characterized by a marked reduction in granule numbers. Although the proliferative response to recombinant thrombopoietin is intact, this is not accompanied by correction of the differentiation defect. Absence of the smaller (p18) subunit of NF-E2 does not have similar consequences. These findings implicate target genes of the NF-E2 transcription factor in critical aspects of late megakaryocyte maturation and platelet formation.
Shivdasani
R A
RA
Department of Medicine, The Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics; D050985:MafK Transcription Factor; D008533:Megakaryocytes / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D016296:Mutagenesis; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D013234:Stem Cells / Q000378:metabolism; D013921:Thrombocytopenia / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050985:MafK Transcription Factor; C494696:Mafk protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D014157:Transcription Factors; D005914:Globins