Expression of C/EBPβ from the C/ebpα gene locus is sufficient for normal hematopoiesis in vivo

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Abstract
CCAAT/enhancer-binding proteins (C/EBPs) are critical transcriptional regulators of differentiation of hematopoietic cells. Previous studies have shown that targeted disruption of theC/ebpα 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/EBPβ was expressed from the C/ebpα gene locus of C/EBPα-null mice, we have evaluated the ability of C/EBPβ to function for C/EBPα 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/EBPβ 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/EBPβ knockin and wild-type mice. These results imply that C/EBPβ can substitute for C/EBPα during hematopoiesis when expressed from the C/ebpα gene locus.