These VEGF120 mice express a VEGF isoform that lacks exons 6 and 7 (including the extracellular matrix binding structures) resulting in a protein that is highly soluble. Most homozygotes die shortly after birth and exhibit severe retinal vascular defects, delayed periendothelial cell recruitment and reduced numbers of pericytes. This mutant mouse strain may be useful in studies of retinal vascular outgrowth and patterning.
Patricia D'Amore, Schepens Eye Research Institute
Heterozygote: Heterozygous mice are viable, fertile and normal in size .
Homozygote: These VEGF120 mice express a VEGF isoform that lacks exons 6 and 7 (including the extracellular matrix binding structures) resulting in a protein that is highly soluble. The majority of homozygous pups die shortly after birth due to cardiorespiratory distress; survivors do not live beyond two weeks of age due to impaired angiogenesis resulting in cardiac failure. Homozygotes exhibit severe retinal vascular defects including a primitive vascular labyrinth at post natal day 5 (P5), delayed periendothelial cell recruitment and reduced numbers of pericytes. In mice that survive to P9, the capillary bed covers two thirds of the retina. Arteriole and venule development is reduced and capillary number is increased. Capillaries are dilated and fragile resulting in hemorrhages. Hyaloid arteries appear dilated and tortuous with no connections to the retinal vasculature. Hyaloid regression is not observed by P9. Numbers of renal and cornary arteries are reduced. This mutant mouse strain may be useful in studies of retinal vascular outgrowth and patterning.
The Donating Investigator reports that very few mice survive beyond post natal day 1.
A targeting vector containing a loxP-flanked neomycin cassette was used to replace exons 6 and 7. 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 VEGF 120 isoform lacks exons 6 and 7, which includes the extracellular matrix binding structures and is highly soluble. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Peter Carmeliet|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Vegfa, vascular endothelial growth factor A|
|Gene Synonym(s)||MVCD1; VEGF; VEGF-A; VEGF120; VEGF164; VEGF188; VPF; Vegf; Vegf; vascular endothelial growth factor|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||Replacement of exons 6 and 7 with a lox-P flanked neomycin cassette. The neomycin cassette was removed prior to blastocyst injection by Cre-mediated recombination in ES cells, resulting in the final allele. A highly soluble isoform of the encoded protein is expressed from this allele.|
|Mutations Made By|| |
Dr. Peter Carmeliet, University of Leuven
When maintaining a live colony, these mice may be bred as heterozygotes. Most homozygotes die shortly after birth due to cardiorespiratory distress, survivors die within two weeks of age due to cardiac failure.
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