title: Abnormal differentiation of erythroid precursors in p45 NF-E2(-/-) mice.
abstract: The transcription factor p45 nuclear factor-erythroid-derived 2 (NF-E2) plays major roles in erythroid and megakaryocytic lineages. Here, we investigated the role of p45 NF-E2 in erythroid differentiation in vivo. Absence of p45 NF-E2 in mice leads to a twofold increase in serum erythropoietin levels. In the bone marrow of these animals, we found a different distribution of precursor populations compared to wild-type mice, suggesting abnormal differentiation. Loss of p45 NF-E2 was also associated with an increase in splenic erythropoiesis, as evidenced by an accumulation of early precursors, namely, late basophilic and polychromatic erythroblasts. These observations are consistent with a stress erythropoiesis phenotype and indicate that the spleen is likely compensating for ineffective erythropoiesis in the bone marrow. Analysis of bone marrow samples revealed increased GATA1 levels, as well as an increased proportion of erythroid cells arrested at the G(1) stage of cell cycle in p45 NF-E2-deficient mice. These results suggest that p45 NF-E2 is required for the differentiation of erythroid precursors.
authors.affiliation: Lady Davis Institute for Medical Research and Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Québec, Canada.
authors.forename: Jadwiga J
authors.initials: JJ
authors.lastname: Gasiorek
authors.forename: Zaynab
authors.initials: Z
authors.lastname: Nouhi
authors.forename: Volker
authors.initials: V
authors.lastname: Blank
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001789:Blood Group Antigens / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D004900:Erythroblasts / Q000473:pathology; D015672:Erythroid Precursor Cells / Q000473:pathology*; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology*; D004921:Erythropoietin / Q000097:blood; D016193:G1 Phase; D050982:GATA1 Transcription Factor / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D011990:Receptors, Transferrin / Q000032:analysis; D013154:Spleen / Q000473:pathology
chemical_list: D015703:Antigens, CD; D001789:Blood Group Antigens; C068126:CD71 antigen; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D011990:Receptors, Transferrin; C489122:TER-119 antigen, mouse; D004921:Erythropoietin