JAX Mouse Strain Datasheet - 027315

STOCK Vegfa^tm2.1Nagy/J

Stock No:: 027315 |; VEGF^hypo

Targeted Mutation

Cryo Recovery

Overview

Also Known As: VEGF^hypo

This VEGF-A hypomorphic strain, VEGF^lo, has reduced expression of Vegfa and functions as a reporter strain for VEGF positive cells and tissues during embryonic vascular development.

Donating Investigator

Andras Nagy, Lunenfeld-Tanenbaum Research Institute (LTRI), Mount Sinai Hospital

Genetic overview

Genetic Background	Generation

Vegfa^tm2.1Nagy

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout, Reporter)	Vegfa	vascular endothelial growth factor A

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Research Applications

Cardiovascular Research
Developmental Biology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

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 VEGF^hypo (VEGF^lo) 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.

Development

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.

Expression Data

Expressed Gene	Vegfa, vascular endothelial growth factor A, mouse, laboratory
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	Endothelial cells

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Damert A; Miquerol L; Gertsenstein M; Risau W; Nagy A. 2002. Insufficient VEGFA activity in yolk sac endoderm compromises haematopoietic and endothelial differentiation. Development 129(8):1881-92. PubMed: 11934854 MGI: J:75937

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Genetics

Vegfa^tm2.1Nagy

Allele Symbol: Vegfa^tm2.1Nagy

Allele Name	targeted mutation 2.1, Andras Nagy
Allele Type	Targeted (Null/Knockout, Reporter)
Allele Synonym(s)	VEGF^hypo; Vegf^lo
Gene Symbol and Name	Vegfa, vascular endothelial growth factor A
Gene Synonym(s)	MVCD1; VEGF; VEGF-A; VEGF111; VEGF120; VEGF164; VEGF188; VPF; Vegf; Vegf; vascular endothelial growth factor
Expressed Gene	Vegfa, vascular endothelial growth factor A, mouse, laboratory
Expressed Gene	lacZ, beta-galactosidase, E. coli
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 Vegf1^tm2Nagy where the floxed PGK-neo cassette in exon 8 has been removed by mating to a cre deletor strain.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Cardiovascular Research
- Heart Abnormalities
- Other
- Vascular Defects
Developmental Biology Research
- Embryonic Lethality (Homozygous)
- Internal/Organ Defects
  - heart: vasculature
  - vasculature
Research Tools
- Cardiovascular Research
- Genetics Research
  - Tissue/Cell Markers: endothelial cells

Mammalian Phenotype Terms by Genotype

Genotype: Vegfa^tm2.1Nagy/Vegfa^tm2.1Nagy
involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

embryonic lethality between somite formation and embryo turning, complete penetrance
- die between E8.5 and E9

embryo phenotype

abnormal vitelline vasculature morphology
- disorganized yolk sac vasculature with large lacunae
- reduction in the number of blood islands devoid of primitive erythrocytes

cardiovascular system phenotype

abnormal dorsal aorta morphology
- reduced lumina of the dorsal aortae

abnormal vitelline vasculature morphology
- disorganized yolk sac vasculature with large lacunae
- reduction in the number of blood islands devoid of primitive erythrocytes

decreased vascular endothelial cell number
- lack mature endothelial cells as indicated by the severely reduced expression of Flt1 (Vegf-R1)

delayed heart development
- development of the heart is delayed
- however, the endocardium is formed

hematopoietic system phenotype

pancytopenia
- lack mature hematopoietic cells as indicated by the severely reduced expression of Klf1 (Eklf)
- reduction in the number of blood cells in the embryo proper, particularly in the sinus venosus

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Vegfa^tm2.1Nagy/Vegfa⁺
involves: 129S1/Sv * 129X1/SvJ

cardiovascular system phenotype

abnormal brain vasculature morphology
- at P1, mice exhibit a decrease in the number of branch points of blood vessels in the forebrain and cortex while the distance between branch points is increased compared with wild-type mice

abnormal vascular branching morphogenesis
- at P1, mice exhibit a decrease in the number of branch points of blood vessels in the forebrain and cortex while the distance between branch points is increased compared with wild-type mice

nervous system phenotype

abnormal brain vasculature morphology
- at P1, mice exhibit a decrease in the number of branch points of blood vessels in the forebrain and cortex while the distance between branch points is increased compared with wild-type mice

References

Damert A; Miquerol L; Gertsenstein M; Risau W; Nagy A. 2002. Insufficient VEGFA activity in yolk sac endoderm compromises haematopoietic and endothelial differentiation. Development 129(8):1881-92. PubMed: 11934854 MGI: J:75937

Additional - Vegfa^tm2.1Nagy related

Clayton JA; Chalothorn D; Faber JE. 2008. Vascular endothelial growth factor-A specifies formation of native collaterals and regulates collateral growth in ischemia. Circ Res 103(9):1027-36. PubMed: 18802023 MGI: J:155294
Coultas L; Nieuwenhuis E; Anderson GA; Cabezas J; Nagy A; Henkelman RM; Hui CC; Rossant J. 2010. Hedgehog regulates distinct vascular patterning events through VEGF-dependent and -independent mechanisms. Blood 116(4):653-60. PubMed: 20339091 MGI: J:162821
Duan LJ; Nagy A; Fong GH. 2003. Gastrulation and angiogenesis, not endothelial specification, is sensitive to partial deficiency in vascular endothelial growth factor-a in mice. Biol Reprod 69(6):1852-8. PubMed: 12890722 MGI: J:86673
Eremina V; Cui S; Gerber H; Ferrara N; Haigh J; Nagy A; Ema M; Rossant J; Jothy S; Miner JH; Quaggin SE. 2006. Vascular endothelial growth factor a signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol 17(3):724-35. PubMed: 16436493 MGI: J:129132
Haigh JJ; Morelli PI; Gerhardt H; Haigh K; Tsien J; Damert A; Miquerol L; Muhlner U; Klein R; Ferrara N; Wagner EF; Betsholtz C; Nagy A. 2003. Cortical and retinal defects caused by dosage-dependent reductions in VEGF-A paracrine signaling. Dev Biol 262(2):225-41. PubMed: 14550787 MGI: J:86207
Lucitti JL; Mackey JK; Morrison JC; Haigh JJ; Adams RH; Faber JE. 2012. Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17. Circ Res 111(12):1539-50. PubMed: 22965144 MGI: J:212884
Martin R; Lahlil R; Damert A; Miquerol L; Nagy A; Keller G; Hoang T. 2004. SCL interacts with VEGF to suppress apoptosis at the onset of hematopoiesis. Development 131(3):693-702. PubMed: 14729577 MGI: J:96898

Pricing & Availability

Cryo Recovery

Domestic
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Vegfa<tm2.1Nagy>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Also Known As: VEGFhypo

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Vegfatm2.1Nagy

Allele Symbol: Vegfatm2.1Nagy

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Vegfatm2.1Nagy/Vegfatm2.1Nagyinvolves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

embryo phenotype

cardiovascular system phenotype

hematopoietic system phenotype

Genotype: Vegfatm2.1Nagy/Vegfa+involves: 129S1/Sv * 129X1/SvJ

cardiovascular system phenotype

nervous system phenotype

References

Additional - Vegfatm2.1Nagy related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: VEGF^hypo

Vegfa^tm2.1Nagy

Allele Symbol: Vegfa^tm2.1Nagy

Genotype: Vegfa^tm2.1Nagy/Vegfa^tm2.1Nagy
involves: 129S1/Sv * 129X1/SvJ * CD-1

Genotype: Vegfa^tm2.1Nagy/Vegfa⁺
involves: 129S1/Sv * 129X1/SvJ

Additional - Vegfa^tm2.1Nagy related