title: Vascular endothelial tyrosine phosphatase (VE-PTP)-null mice undergo vasculogenesis but die embryonically because of defects in angiogenesis.
abstract: Development of the vascular system depends on the highly coordinated actions of a variety of angiogenic regulators. Several of these regulators are members of the tyrosine kinase superfamily, including VEGF receptors and angiopoietin receptors, Tie1 and Tie2. Tyrosine kinase signaling is counter-regulated by the activity of tyrosine phosphatases, including vascular endothelial protein tyrosine phosphatase (VE-PTP), which has previously been shown to modulate Tie2 activity. We generated mice in which VE-PTP is replaced with a reporter gene. We confirm that VE-PTP is expressed in endothelium and also show that VE-PTP is highly expressed in the developing outflow tract of the heart and later is expressed in developing heart valves. Vasculogenesis occurs normally in mice lacking VE-PTP; however, angiogenesis is abnormal. Angiogenic defects in VE-PTP-null mice were most pronounced in the yolk sac and include a complete failure to elaborate the primitive vascular scaffold into higher-order branched arteries, veins, and capillaries. VE-PTP continues to be expressed into adulthood in the vasculature and heart valves, suggesting later roles in vascular development or homeostasis. VE-PTP is also expressed in the vasculature of growing tumors, suggesting that VE-PTP may be a new potential target for angiogenic therapies.
authors.affiliation: Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Dominguez
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Hughes
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Mary
authors.initials: M
authors.lastname: Simmons
authors.forename: Christopher
authors.initials: C
authors.lastname: Daly
authors.forename: Keith
authors.initials: K
authors.lastname: Anderson
authors.forename: Irene
authors.initials: I
authors.lastname: Noguera-Troise
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Samuel
authors.initials: S
authors.lastname: Davis
authors.forename: Gavin
authors.initials: G
authors.lastname: Thurston
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gale
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers; D042783:Endothelial Cells / Q000378:metabolism*; D017353:Gene Deletion; D018390:Gene Targeting; D006351:Heart Valves / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015017:Yolk Sac / Q000098:blood supply* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D017027:Protein Tyrosine Phosphatases; C516887:Ptprb protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3