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International Journal of Hematology

, Volume 73, Issue 4, pp 463–468 | Cite as

Defective Megakaryopoiesis and Abnormal Erythroid Development inFli-1 Gene-Targeted Mice

  • Hiroshi Kawada
  • Tatsuya Ito
  • Pamela N. Pharr
  • Demetri D. Spyropoulos
  • Dennis K. Watson
  • Makio Ogawa
Rapid Communication

Abstract

Mouse embryos homozygous for a targeted disruption in theFli-1 gene show hemorrhage into the neural tube and brain on embryonic day (E)11.0 and die shortly thereafter. Livers from the mutant embryos contain drastically reduced numbers of pronormoblasts, basophilic normoblasts, and colony-forming cells.To determine the nature of impaired hematopoiesis, we carried out cell culture studies of mutant embryonic stem (ES) cells and cells from the aorta-gonad-mesonephros (AGM) region of E10.0 mutant embryos. There was a striking reduction in the number of megakaryocytes in cultures of mutant AGM cells compared with cultures of AGM cells from wild-type or heterozygous embryos. Furthermore,Fli-1 mutant ES cells failed to produce megakaryocyte colonies and multilineage colonies containing megakaryocytes. Consistent with the observed defect in megakaryopoiesis, we also demonstrated the down-regulation of c-mpl in the AGM of mutant embryos. The percentages of pronormoblasts and basophilic normoblasts were significantly reduced in cultures of mutant AGM embryos, which contained primarily polychromatophilic and orthochromatic normoblasts. These results provide further evidence for the role ofFli-1 in the regulation of hematopoiesis and for c-mpl as aFli-1 target gene.

Key words

Fli-1 Megakaryocyte Hematopoiesis c-mpl 

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Copyright information

© The Japanese Society of Hematology 2001

Authors and Affiliations

  • Hiroshi Kawada
    • 1
  • Tatsuya Ito
    • 1
  • Pamela N. Pharr
    • 1
  • Demetri D. Spyropoulos
    • 1
  • Dennis K. Watson
    • 1
  • Makio Ogawa
    • 1
  1. 1.Department of Medicine, Laboratory of Cancer GenomicsHollings Cancer Center, Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical CenterCharlestonUSA

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