Retinal arterial development in VEGF188 mice is impaired. Homozygotes exhibit reduced fertility, smaller litter sizes and some prenatal lethality. This mutant mouse strain may be useful in studies of retinal angiogenesis.
Patricia D'Amore, Schepens Eye Research Institute
Heterozygote: Heterozygote phenotype is similar to the wild-type phenotype.
Homozygote: Mice homozygous for the targeted mutation are viable, but exhibit reduced fertility, smaller litter sizes and some prenatal lethality. Surviving homozygotes gain less weight than wild-type controls. Retinal arterial development in VEGF188 mice is impaired. By post natal day 5 (P5), only half the normal number of large vessels (mostly venules) are present in the vascular bed of the retina. By P9, arterioles are observed to be smaller in size and only 50% have developed and grown out over 17% of the retina. In controls, 88% of the retinal radius is covered by P9. Venous and capillary development appears normal.
VEGF188 mice express a VEGF protein with all eight exons that avidly binds to the cell surface and extracellular matrix. This mutant mouse strain may be useful in studies of retinal angiogenesis.
A targeting vector was designed to insert a loxP-flanked neomycin cassette into the 3' UTR of a cDNA containing fused exons 4 through 8. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1 derived R1 embryonic stem (ES) cells. Transient Cre expression in targeted cells excised the neo cassette. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred to C57BL/6 and then maintained by sibling mating. The VEGF188 isoform contains all 8 exons. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 4, Peter Carmeliet|
|Gene Symbol and Name||Vegfa, vascular endothelial growth factor A|
|Promoter||Vegfa, vascular endothelial growth factor A, mouse, laboratory|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Genomic sequence containing exons 4 through 8 was replaced with corresponding cDNA. The resultant allele lacks splice sites and thereby produces a single isoform with high receptor binding properties. The exclusive presence of this isoform was verified by quatitative RT-PCR.|
|Mutations Made By|| |
Dr. Peter Carmeliet, University of Leuven
When maintaining a live colony, these mice can be bred as heterozygotes or homozygotes, however, homozygotes occur at a lower than Mendelian ratio (12%) than expected.
When using the B6;129-Vegfatm4Pec/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34406 in your Materials and Methods section.