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Blood, 1 January 2005, Vol. 105, No. 1, pp. 95-102.
Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2003-12-4345.
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Submitted December 22, 2003
Accepted August 1, 2004
Dysregulation of granulocyte, erythrocyte and NK cell lineages in Fli-1 gene targeted mice
Masahiro Masuya, Omar Moussa, Takanori Abe, Takao Deguchi, Tsukasa Higuchi, Yasuhiro Ebihara, Demetri D Spyropoulos, Dennis K Watson, and Makio Ogawa*
Department of Veterans Affairs Medical Center, Charleston, SC, USA; Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
Department of Pathology, Medical University of South Carolina, Charleston, SC, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA
Department of Pathology, Medical University of South Carolina, Charleston, SC, USA; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA
* Corresponding author; email: ogawam{at}musc.edu.
Targeted disruption of Fli-1 proto-oncogene results in severe dysmegakaryopoiesis and embryonic lethality. We used morula-stage aggregation as a strategy to clarify further the hematopoietic defects of the Fli-1 gene-targeted mice. Analyses of lineage expression of Fli-1+/- and Fli-1-/- cells in the peripheral blood and bone marrow of chimeric mice consistently demonstrated reduced numbers of neutrophilic granulocytes and monocytes and increased numbers of NK cells. Transplantation studies using sorted Fli-1 mutant cells produced similar findings. Clonal culture studies of bone marrow cells revealed increased numbers of granulocytic and early erythroid progenitors in the Fli-1+/- cells. The sorted Fli-1-/- bone marrow cells revealed specific down-regulation of C/EBP and C/EBP , and the receptors for G-CSF and GM-CSF, consistent with their critical roles in granulopoiesis. Collectively, these observations suggest previously unknown physiological roles for Fli-1 in granulocytic, erythroid and NK cell proliferation and differentiation. Production of chimeras by morula-stage embryo aggregation is an effective way to unravel cell-autonomous hematopoietic defects in gene-targeted mice.

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