Abstract
The murine VEGF gene is alternatively transcribed to yield the VEGF(120), VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF(120/120) mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF(164), was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Arterioles / abnormalities
- Arterioles / growth & development
- Base Sequence
- Body Patterning / genetics
- Body Patterning / physiology
- DNA / genetics
- Endothelial Growth Factors / genetics*
- Endothelial Growth Factors / physiology*
- Female
- Gene Expression Regulation, Developmental
- Gene Targeting
- Lymphokines / genetics*
- Lymphokines / physiology*
- Male
- Mice
- Mice, Transgenic
- Pregnancy
- Protein Isoforms / genetics
- Protein Isoforms / physiology
- Receptor Protein-Tyrosine Kinases / genetics
- Receptors, Growth Factor / genetics
- Receptors, Vascular Endothelial Growth Factor
- Retinal Vessels / abnormalities
- Retinal Vessels / growth & development*
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Venules / abnormalities
- Venules / growth & development
Substances
- Endothelial Growth Factors
- Lymphokines
- Protein Isoforms
- Receptors, Growth Factor
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- DNA
- Receptor Protein-Tyrosine Kinases
- Receptors, Vascular Endothelial Growth Factor