title: Expression of C/EBPbeta from the C/ebpalpha gene locus is sufficient for normal hematopoiesis in vivo.
abstract: CCAAT/enhancer-binding proteins (C/EBPs) are critical transcriptional regulators of differentiation of hematopoietic cells. Previous studies have shown that targeted disruption of the C/ebpalpha gene results in a lack of granulocytic differentiation with an arrest at the stage of immature myeloblasts. By using a gene replacement strategy in which C/EBPbeta was expressed from the C/ebpalpha gene locus of C/EBPalpha-null mice, we have evaluated the ability of C/EBPbeta to function for C/EBPalpha in directing differentiation along the granulocytic pathway. We show that the morphology and the differential cell counts of the bone marrow and peripheral blood cells from C/EBPbeta knockin mice are indistinguishable from those of their wild-type littermates, indicating that hematopoiesis occurs normally in these animals. Additionally, we analyzed expression of 21 myeloid-specific genes, including markers for distinct stages of granulocytic differentiation, and found no significant differences in their levels of expression in the bone marrow of C/EBPbeta knockin and wild-type mice. These results imply that C/EBPbeta can substitute for C/EBPalpha during hematopoiesis when expressed from the C/ebpalpha gene locus.
authors.affiliation: Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd, Rm. 109, Los Angeles, CA 90048, USA. Letetia.Jones@cshs.org
authors.forename: Letetia C
authors.initials: LC
authors.lastname: Jones
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Lin
authors.forename: Shih-Shun
authors.initials: SS
authors.lastname: Chen
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
authors.forename: Wolf-K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.forename: Ying-Hue
authors.initials: YH
authors.lastname: Lee
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D012333:RNA, Messenger