Fli-1 Is Required for Murine Vascular and Megakaryocytic Development and Is Hemizygously Deleted in Patients with Thrombocytopenia

• Published in: Immunity (Cambridge, Mass.) Mass.), 2000-08, Vol.13 (2), p.167-177
• Main Authors: Hart, Adam, Melet, Fabrice, Grossfeld, Paul, Chien, Kenneth, Jones, Christopher, Tunnacliffe, Alan, Favier, Remi, Bernstein, Alan
• Format: Article
• Language: English
• Subjects: angiopoietin 1; Animals; Blood Vessels - embryology; Blood Vessels - pathology; Blood Vessels - physiology; Cell Differentiation - genetics; DNA-Binding Proteins - genetics; Embryonic and Fetal Development - genetics; Fli-1 gene; 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
• ISSN: 1074-7613; 1097-4180
• 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.