title: Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia.
abstract: 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.
authors.affiliation: Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. hart@mshri.on.ca
authors.forename: A
authors.initials: A
authors.lastname: Hart
authors.forename: F
authors.initials: F
authors.lastname: Melet
authors.forename: P
authors.initials: P
authors.lastname: Grossfeld
authors.forename: K
authors.initials: K
authors.lastname: Chien
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Tunnacliffe
authors.forename: R
authors.initials: R
authors.lastname: Favier
authors.forename: A
authors.initials: A
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000473:pathology* / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators