Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Wild-type x Heterozygote         (Female x Male)   13-JAN-12 Mating System Heterozygote x Wild-type         (Female x Male)   13-JAN-12 Species laboratory mouse Generation ?+F2 (08-JAN-13) Generation Definitions   Donating Investigator Dr. Janet Rossant,   The Hospital for Sick Children

Description
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygotes have an embryonic lethal phenotype, failing to develop past approximately 9.5dpc due to the lack of hematopoietic and endothelial cells. Fluorescence in heterozygous embryos is detected as early as the primitive streak stage and mimics the endogenous gene expression pattern.

Development
A targeting vector containing eGFP, and a loxP site flanked PGK-NEO cassette, was used to disrupt exon 1. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to Cre deleter strain to remove the floxed selection cassette. The mice were then crossed to ICR mice. Upon arrival at The Jackson Laboratory, the mice were crossed to ICR/HaJ mice (Stock No. 009122) at least once to establish the colony.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Kdr

002938	B6.129-Kdrtm1Jrt/J
018542	FVB-Tg(Kdr-mCherry)1Medi/J
008685	FVB-Tg(tetO-Kdr*)4377.5Rwng/J
017617	FVB/N-Tg(Kdr-TVA)1026Ebp/J
018976	STOCK Kdrtm1(cre)Sato/J
018977	STOCK Kdrtm2Sato/J

View Strains carrying other alleles of Kdr     (6 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Hemangioma, Capillary Infantile   (KDR)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Kdr^tm2.1Jrt/Kdr⁺

        involves: 129S1/Sv * 129X1/SvJ

• no phenotypic analysis
• *normal* no phenotypic analysis
  • only EGFP expression is analyzed   (MGI Ref ID J:109435)

View Research Applications

Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)

Research Tools
Fluorescent Proteins

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Kdrtm2.1Jrt
Allele Name		targeted mutation 2.1, Janet Rossant
Allele Type		Targeted (Reporter)
Common Name(s)		Flk1-EGFP(neo out); Flk1-GFP; VEGFR2-GFP;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Site of Expression		GFP is expressed in hematopoietic and endothelial cells as early as the primitive streak stage.
Gene Symbol and Name		Kdr, kinase insert domain protein receptor
Chromosome		5
Gene Common Name(s)		CD309; FLK1; Flk-1; Flk1; VEGF receptor-2; VEGFR; VEGFR-2; VEGFR2; fetal liver kinase 1; vascular endothelial growth factor receptor- 2;
Molecular Note		An in-frame EGFP cDNA gene and a floxed PGK-neomycin resistance cassette replaced the translated portion of the first coding exon and the proximal part of the next intron, and placed EGFP under the transcriptional control of the endogenous promoter. The floxed PGK-neomycin promoter was subsequently removed by crossing to a cre-deleter strain. [MGI Ref ID J:109435]

Genotyping

Genotyping Information

Genotyping Protocols

Kdr^tm2.1Jrt, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ema M; Takahashi S; Rossant J. 2006. Deletion of the selection cassette, but not cis-acting elements, in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors. Blood 107(1):111-7. [PubMed: 16166582]  [MGI Ref ID J:109435]

Additional References

Kdr^tm2.1Jrt related

Cui S; Li C; Ema M; Weinstein J; Quaggin SE. 2005. Rapid isolation of glomeruli coupled with gene expression profiling identifies downstream targets in Pod1 knockout mice. J Am Soc Nephrol 16(11):3247-55. [PubMed: 16207825]  [MGI Ref ID J:116843]

Ding BS; Nolan DJ; Butler JM; James D; Babazadeh AO; Rosenwaks Z; Mittal V; Kobayashi H; Shido K; Lyden D; Sato TN; Rabbany SY; Rafii S. 2010. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature 468(7321):310-5. [PubMed: 21068842]  [MGI Ref ID J:166849]

Ema M; Yokomizo T; Wakamatsu A; Terunuma T; Yamamoto M; Takahashi S. 2006. Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin, and CD34 in the mouse embryo. Blood 108(13):4018-24. [PubMed: 16926294]  [MGI Ref ID J:140543]

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 Ref ID J:129132]

Hooper AT; Butler JM; Nolan DJ; Kranz A; Iida K; Kobayashi M; Kopp HG; Shido K; Petit I; Yanger K; James D; Witte L; Zhu Z; Wu Y; Pytowski B; Rosenwaks Z; Mittal V; Sato TN; Rafii S. 2009. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell 4(3):263-74. [PubMed: 19265665]  [MGI Ref ID J:149917]

Ishitobi H; Wakamatsu A; Liu F; Azami T; Hamada M; Matsumoto K; Kataoka H; Kobayashi M; Choi K; Nishikawa S; Takahashi S; Ema M. 2011. Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse. Development 138(24):5357-68. [PubMed: 22071109]  [MGI Ref ID J:178675]

Jeansson M; Gawlik A; Anderson G; Li C; Kerjaschki D; Henkelman M; Quaggin SE. 2011. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest 121(6):2278-89. [PubMed: 21606590]  [MGI Ref ID J:174022]

Okuno Y; Nakamura-Ishizu A; Kishi K; Suda T; Kubota Y. 2011. Bone marrow-derived cells serve as proangiogenic macrophages but not endothelial cells in wound healing. Blood 117(19):5264-72. [PubMed: 21411758]  [MGI Ref ID J:173270]

Ruiz de Almodovar C; Coulon C; Salin PA; Knevels E; Chounlamountri N; Poesen K; Hermans K; Lambrechts D; Van Geyte K; Dhondt J; Dresselaers T; Renaud J; Aragones J; Zacchigna S; Geudens I; Gall D; Stroobants S; Mutin M; Dassonville K; Storkebaum E; Jordan BF; Eriksson U; Moons L; D'Hooge R; Haigh JJ; Belin MF; Schiffmann S; Van Hecke P; Gallez B; Vinckier S; Chedotal A; Honnorat J; Thomasset N; Carmeliet P; Meissirel C. 2010. Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. J Neurosci 30(45):15052-66. [PubMed: 21068311]  [MGI Ref ID J:166454]

Sison K; Eremina V; Baelde H; Min W; Hirashima M; Fantus IG; Quaggin SE. 2010. Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling. J Am Soc Nephrol 21(10):1691-701. [PubMed: 20688931]  [MGI Ref ID J:185910]

Takase H; Matsumoto K; Yamadera R; Kubota Y; Otsu A; Suzuki R; Ishitobi H; Mochizuki H; Kojima T; Takano S; Uchida K; Takahashi S; Ema M. 2012. Genome-wide identification of endothelial cell-enriched genes in the mouse embryo. Blood 120(4):914-23. [PubMed: 22535667]  [MGI Ref ID J:188649]

Xu K; Sacharidou A; Fu S; Chong DC; Skaug B; Chen ZJ; Davis GE; Cleaver O. 2011. Blood vessel tubulogenesis requires Rasip1 regulation of GTPase signaling. Dev Cell 20(4):526-39. [PubMed: 21396893]  [MGI Ref ID J:174152]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes have an embryonic lethal phenotype.
Mating System	Wild-type x Heterozygote         (Female x Male)   13-JAN-12
	Heterozygote x Wild-type         (Female x Male)   13-JAN-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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