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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2032-2036
HEMATOPOIESIS
Expression of C/EBP from the C/ebp gene locus is
sufficient for normal hematopoiesis in vivo
Letetia C. Jones,
Meng-Liang Lin,
Shih-Shun Chen,
Utz Krug,
Wolf-K. Hofmann,
Stephen Lee,
Ying-Hue Lee, and
H. Phillip Koeffler
From the Division of Hematology and Oncology,
Department of Medicine, and the Department of Pathology, Cedars-Sinai
Medical Center, University of California-Los Angeles School of
Medicine; Laboratory of Molecular Pathology, Institute of Molecular
Biology, Academia Sinica, Taipei, Taiwan; School of Medical Technology,
China Medical College, Taichung, Taiwan.
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/ebp 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/EBP was expressed from
the C/ebp gene locus of C/EBP-null mice, we have
evaluated the ability of C/EBP to function for C/EBP 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/EBP 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/EBP knockin and wild-type mice. These results imply that
C/EBP can substitute for C/EBP during hematopoiesis when
expressed from the C/ebp gene locus.
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