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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.
HEMATOPOIESIS Dysregulation of granulocyte, erythrocyte, and NK cell lineages in Fli-1 genetargeted miceFrom the Department of Veterans Affairs Medical Center, Charleston SC; and the Departments of Medicine, Pathology and Biochemistry, and Molecular Biology, and the Hollings Cancer Center, Medical University of South Carolina, Charleston, SC.
Targeted disruption of the Friend leukemia integration 1 (Fli-1) proto-oncogene results in severe dysmegakaryopoiesis and embryonic lethality. We used morula-stage aggregation as a strategy to further clarify 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 natural killer (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 CCAAT/enhancer binding protein-
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