This VEGF-A hypomorphic strain, VEGFlo, has reduced expression of Vegfa and functions as a reporter strain for VEGF positive cells and tissues during embryonic vascular development.
Andras Nagy, Lunenfeld-Tanenbaum Research Institute (LTRI), Mount Sinai Hospital
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Vegfa | vascular endothelial growth factor A |
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.
A targeting vector containing an IRES-lacZ cassette, and floxed PGK-NEO, was inserted into the 3' UTR (noncoding region of exon 8) of the Vegfa gene, directly adjacent to the stop codon. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Chimeric mice were generated by aggregating correctly targeted ES cells with CD-1 morula-stage embryos. The resulting heterozygotes were crossed to CMV-Cre transgenic mice (most likely on the CD-1 genetic background) to remove the loxP site flanked NEO cassette. The mice were then crossed to CD-1.
Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ
(Stock No. 002448) at least once to establish the colony.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Expressed Gene | Vegfa, vascular endothelial growth factor A, mouse, laboratory |
Site of Expression | Endothelial cells |
Allele Name | targeted mutation 2.1, Andras Nagy |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | VEGFhypo; Vegflo |
Gene Symbol and Name | Vegfa, vascular endothelial growth factor A |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Expressed Gene | Vegfa, vascular endothelial growth factor A, mouse, laboratory |
Site of Expression | Endothelial cells |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 17 |
Molecular Note | The mutant is a derivative of Vegf1tm2Nagy where the floxed PGK-neo cassette in exon 8 has been removed by mating to a cre deletor strain. |
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to FVB/NJ inbred mice (Stock No. 001800). Homozygotes are not viable.
When using the VEGFhypo mouse strain in a publication, please cite the originating article(s) and include JAX stock #027315 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Vegfa<tm2.1Nagy> |
Frozen Mouse Embryo | STOCK Vegfa<tm2.1Nagy>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Vegfa<tm2.1Nagy>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Vegfa<tm2.1Nagy>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Vegfa<tm2.1Nagy>/J Frozen Embryo | $3373.50 |
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