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 InstituteRead More +
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.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.