title: Endothelium-specific overexpression of human vascular endothelial growth factor-D in mice leads to increased tumor frequency and a reduced lifespan.
abstract: BACKGROUND
  Vascular endothelial growth factors (VEGFs) are central mediators in vascular development and lymphangiogenesis. VEGF-D contributes to the growth and formation of blood and lymphatic vessels, although its biological role is still somewhat unclear.
  
  
  METHODS
  Transgenic mice, which express the mature form of human VEGF-D under endothelium-specific Tie1 promoter, were produced by the lentiviral perivitelline-injection method. The mice were followed up to generation F(5) and the effect of the transgene was analyzed.
  
  
  RESULTS
  Transgenic mice had a high expression of human (h)VEGF-D in the endothelium in several tissues, such as kidney, liver, lung and spleen. However, transgenic mice developed tumors in lungs, kidneys, liver, mammary glands and lymph nodes upon aging and their mortality was also increased as a result of other pathological conditions. Hind limb ischemia was surgically induced in these mice and they were analyzed 1, 2 and 3  weeks after the ischemia operation. No significant differences were found in hVEGF-D mRNA expression, the number of capillaries or tissue repair between ischemic transgenic mice and transgene negative littermates.
  
  
  CONCLUSIONS
  It is concluded that targeted unregulated long-term expression of hVEGF-D in endothelium may not be useful and reduces the life span of transgenic mice.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Antti A
authors.initials: AA
authors.lastname: Kotimaa
authors.forename: Anna-Mari
authors.initials: AM
authors.lastname: Zainana
authors.forename: Eveliina
authors.initials: E
authors.lastname: Pulkkinen
authors.forename: Jenni
authors.initials: J
authors.lastname: Huusko
authors.forename: Suvi E
authors.initials: SE
authors.lastname: Heinonen
authors.forename: Ivana
authors.initials: I
authors.lastname: Kholová
authors.forename: Hanna
authors.initials: H
authors.lastname: Stedt
authors.forename: Hanna P
authors.initials: HP
authors.lastname: Lesch
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004727:Endothelium / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism*; D016086:Lentivirus; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D042810:Receptor, TIE-1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics* / Q000378:metabolism*
chemical_list: D042643:Vascular Endothelial Growth Factor D; D042810:Receptor, TIE-1