Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia

Immunity. 2000 Aug;13(2):167-77. doi: 10.1016/s1074-7613(00)00017-0.


The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebral meninges and specific downregulation of Tek/Tie-2, the receptor for angiopoietin-1. We also show that dysmegakaryopoiesis in Fli-1 null embryos resembles that frequently seen in patients with terminal deletions of 11q (Jacobsen or Paris-Trousseau Syndrome). We map the megakaryocytic defects in 14 Jacobsen patients to a minimal region on 11q that includes the Fli-1 gene and suggest that dysmegakaryopoiesis in these patients may be caused by hemizygous loss of Fli-1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Vessels / embryology
  • Blood Vessels / pathology*
  • Blood Vessels / physiology*
  • Cell Differentiation / genetics
  • DNA-Binding Proteins / genetics*
  • Embryonic and Fetal Development / genetics
  • Gene Deletion
  • Gene Expression Regulation, Developmental / physiology*
  • Humans
  • Megakaryocytes / pathology*
  • Megakaryocytes / physiology*
  • Mice
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins*
  • Thrombocytopenia / genetics*
  • Thrombocytopenia / pathology
  • Thrombocytopenia / physiopathology
  • Trans-Activators / genetics*


  • DNA-Binding Proteins
  • Fli1 protein, mouse
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins
  • Trans-Activators