Vascular endothelial growth factor A is a mitogenic glycoprotein specific for endothelial cells and is involved in vascular permeability, angiogenesis, vasculogenesis, cell migration, as well as endothelial cell growth. These VEGFhypo (VEGFlo) mice carry an IRES-beta-galactosidase knock in mutation of the Vegfa gene. Mutant mRNA is detected by RT-PCR analysis of homozygous embryos. The last six C-terminal amino acid residues of the protein, encoded by exon 8, are replaced by 66 amino acids encoded by lacZ. Other aberrant splicing events are also detected. VEGF-A protein activity is significantly reduced (25 % to 50%) in heterozygotes compared to controls, as determined by RT-PCR of calf and collateral zone adductor muscles.
Mice that are homozygous for the targeted knock-in allele have an embryonic lethal phenotype, dying between 9.5 and 11.0 dpc due to systemic cardiovascular defects. Homozygous embryos exhibit disorganized yolk sac vasculature, delayed heart development, reduced dorsal aorta lumen, fewer vascular endothelial cells, and pancytopenia (reduced number of blood cells). Mice that are heterozygous for the targeted mutation are viable and fertile. Heterozygotes exhibit reduced angiogenic sprouting during development. After hindlimb ischemia or cerebral artery ligation, heterozygotes have lower perfusion with diminished recovery, collateral remodeling, and angiogenesis compared to wildtype controls.
Beta-galactosidase activity is similar to that observed in the VEGF-LacZ KI-Δneo strain (Stock No. 027314).
The lacZ reporter expression mimics the endogenous Vegfa gene expression pattern during development and adulthood.
