Angiogenesis

, Volume 9, Issue 4, pp 209–224

Unique vascular phenotypes following over-expression of individual VEGFA isoforms from the developing lens

  • Christopher A. Mitchell
  • Catrin S. Rutland
  • Michael Walker
  • Muneeb Nasir
  • Alexander J. E. Foss
  • Christine Stewart
  • Holger Gerhardt
  • Moritz A. Konerding
  • Werner Risau
  • Hannes C. A. Drexler
Original Paper

Abstract

Formation of a correctly organised vasculature and subsequently embryonic survival is critically dependent on the dosage and site-specific expression of VEGF. Murine VEGF exists in three common isoforms (viz. 120, 164 and 188 amino acids) having different organ specific distribution levels. Gene knock-in studies show that expression of any of the individual isoforms of VEGF extends survival until birth, although each is associated with distinct organ-specific abnormalities. Comparison of the effects of VEGF isoform expression is complicated by the general lethality of mis-expression, in addition to cumulative effects of adjacent tissues from the inappropriately patterned vasculature. Here we investigate the effects of over-expression of individual VEGFA isoforms from the lens-specific αA-Crystallin promoter and characterise their effects on the vessel morphology of the hyaloid and developing retinal vasculature. Since the hyaloid vasculature is an anatomically distinct, transient vasculature of the eye, comprising 3 cell types (endothelium, pericytes and macrophages) it is possible to more readily interpret the role of individual VEGF-A isoforms in vascular pattern formation in this model. The severity of the vascular phenotype, characterised by a hyperplastic hyaloid at E13.5 and subsequently retinal vascular patterning and ocular defects, is most severe in transgenics over-expressing the more diffusible forms of VEGFA (120 and 164), whereas in VEGFA188 transgenics the hyaloid vascular defects partially resolve post-natally. The results of this study indicate that individual isoforms of VEGFA induce distinct vascular phenotypes in the eye during embryonic development and that their relative doses provide instructive cues for vascular patterning.

Keywords

Mouse Transgenic Lens Angiogenesis VEGF Isoforms 

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Copyright information

© Springer Science + Business Media B.V. 2006

Authors and Affiliations

  • Christopher A. Mitchell
    • 1
    • 2
    • 3
  • Catrin S. Rutland
    • 1
  • Michael Walker
    • 2
  • Muneeb Nasir
    • 1
  • Alexander J. E. Foss
    • 4
  • Christine Stewart
    • 3
  • Holger Gerhardt
    • 5
  • Moritz A. Konerding
    • 6
  • Werner Risau
    • 2
  • Hannes C. A. Drexler
    • 2
  1. 1.Department of Obstetrics and GynaecologyUniversity of Nottingham, City HospitalNottinghamUK
  2. 2.Max-Planck Institute for Physiology and Clinical Research, W.G. Kerckhoff InstituteBad NauheimGermany
  3. 3.Centre for Molecular Biosciences, School of Biomedical SciencesUniversity of UlsterColeraineUK
  4. 4.Department of OphthalmologyQueens Medical CentreNottinghamUK
  5. 5.Department of Medical BiochemistryGothenburg UniversityGothenburgSweden
  6. 6.Institute of Anatomy and Cell Biology, Macroscopic DepartmentJohannes Gutenberg University MainzMainzGermany

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