Strain Name:

STOCK Flt1tm1Jrt/FongJ

Stock Number:

019457

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 29-DEC-14
Use Restrictions Apply, see Terms of Use
This knock-in/knock-out reporter strain expresses beta-galactosidase in endothelial cells from the endogenous mouse Flt1 locus. They are suitable for use in applications related to the study of vascular development and VEGF-mediated signaling.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemWild-type x Heterozygote         (Female x Male)   06-MAR-14
Mating SystemHeterozygote x Wild-type         (Female x Male)   06-MAR-14
Specieslaboratory mouse
 
Donating Investigator Guo-Hua Fong,   Univ CT Health Center

Description
The Flt1 (FMS-like tyrosine kinase 1) gene encodes a receptor tyrosine kinase that binds to the VEGFR-A, VEGFR-B and placental growth factor proteins and is involved in angiogenesis and vasculogenesis. These mice carry a targeted mutation of the Flt1 gene in which a lacZ-NEO cassette disrupts coding sequence, including the translation start site. Mice that are heterozygous for the targeted mutation are viable and fertile. Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic days 8.5. No gene product is detected by RT-PCR analysis of total RNA from homozygotes. Although homozygous embryos develop more hemangioblasts at E7.0, and primary erythrocytes and endothelial cells at E8.5, they exhibit disorganized blood islands and yolk sac vascular network. In heterozygotes, the beta-galactosidase activity pattern mimics the endogenous gene expression pattern in the embryo and yolk sac with the exception of a loss of expression in spongiotrophoblasts. lacZ expression is detected as early as E6.5, and during development is restricted to endothelial cells. Heterozygotes exhibit impaired recovery from ischemic injury to the myocardium. Heterozygotes exhibit enlarged Schlemm's canals and disorganized sclera collagen fibers.

Development
A targeting vector designed by Drs. Janet Rossant and Guo-Hua Fong (University of Toronto and Mt Sinai Hospital, Toronto) containing a lacZ-NEO cassette was used to disrupt sequence encoding signal peptide, including the translation start site. 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 mice were crossed to C57BL/6 mice, and then crossed to CD1 mice. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Flt1tm1Jrt/Flt1+

        involves: CD-1
  • cardiovascular system phenotype
  • increased response of heart to induced stress
    • mice exhibit decreased ischemic preconditioning-mediated cardioprotection compared with wild-type mice   (MGI Ref ID J:101949)
  • homeostasis/metabolism phenotype
  • increased response of heart to induced stress
    • mice exhibit decreased ischemic preconditioning-mediated cardioprotection compared with wild-type mice   (MGI Ref ID J:101949)

Flt1tm1Jrt/Flt1+

        Background Not Specified
  • cardiovascular system phenotype
  • abnormal blood circulation
    • mice exhibit increased blood perfusion compared with wild-type mice   (MGI Ref ID J:164891)
  • abnormal blood vessel morphology
    • mice exhibit increased vascular density in the tibialis anterior compared with wild-type mice   (MGI Ref ID J:164891)
    • abnormal physiological neovascularization
      • following hind limb ischemia, mice exhibit blood flow and reduced capillary density compared with similarly treated wild-type mice   (MGI Ref ID J:151369)
    • increased angiogenesis
      • mice exhibit increased vascular density in the tibialis anterior compared with wild-type mice   (MGI Ref ID J:164891)

Flt1tm1Jrt/Flt1tm1Jrt

        either: (involves: 129/Sv) or (involves: CD-1) or (involves: ICR)
  • embryogenesis phenotype
  • abnormal embryogenesis/ development
    • at E7.0, mice exhibit increased number of hemangioblasts compared with wild-type mice   (MGI Ref ID J:54830)
    • at E8.5, the number of endothelial cells is increased compared to in wild-type mice   (MGI Ref ID J:54830)
    • at E8.5, mice exhibit an increase in primary erythrocytes compared with wild-type mice   (MGI Ref ID J:54830)
    • altered cell differentiation leads to increased number of hemangioblasts compared to in wild-type mice   (MGI Ref ID J:54830)
    • abnormal embryonic erythrocyte morphology
      • at E8.5, mice exhibit an increase in primary erythrocytes compared with wild-type mice   (MGI Ref ID J:54830)
  • hematopoietic system phenotype
  • abnormal embryonic erythrocyte morphology
    • at E8.5, mice exhibit an increase in primary erythrocytes compared with wild-type mice   (MGI Ref ID J:54830)
  • increased hemangioblast number
    • at E7.0, mice exhibit increased number of hemangioblasts compared with wild-type mice   (MGI Ref ID J:54830)

Flt1tm1Jrt/Flt1tm1Jrt

        Background Not Specified
  • mortality/aging
  • complete embryonic lethality during organogenesis
    • no mice are observed after E9   (MGI Ref ID J:26845)
  • cardiovascular system phenotype
  • abnormal heart development
    • the endocardial lining of heart ventricles are thickened and disorganized compared to in wild-type mice   (MGI Ref ID J:26845)
  • abnormal vascular development
    • only large fused vessels with internally localized groups of endothelial cells are present in the head mesenchyme instead of the small vessels observed in wild-type mice   (MGI Ref ID J:26845)
    • abnormal dorsal aorta morphology
      • contains endothelial cells within the lumen   (MGI Ref ID J:26845)
    • abnormal vitelline vasculature morphology
      • vascular structures are large and enclosed with endothelial cells compared to in wild-type mice   (MGI Ref ID J:26845)
      • however, endothelial cell formation is normal   (MGI Ref ID J:26845)
      • disorganized yolk sac vascular plexus   (MGI Ref ID J:26845)
  • embryogenesis phenotype
  • abnormal visceral yolk sac blood island morphology
    • blood-island structures are abnormal and disorganized compared to in wild-type mice   (MGI Ref ID J:26845)
  • abnormal vitelline vasculature morphology
    • vascular structures are large and enclosed with endothelial cells compared to in wild-type mice   (MGI Ref ID J:26845)
    • however, endothelial cell formation is normal   (MGI Ref ID J:26845)
    • disorganized yolk sac vascular plexus   (MGI Ref ID J:26845)
  • embryonic growth arrest
View Research Applications

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

Cardiovascular Research
Vascular Defects

Developmental Biology Research
Embryonic Lethality (Homozygous)
Eye Defects
Internal/Organ Defects
      heart: vasculature

Research Tools
lacZ Expression
Cardiovascular Research
      endothelial cell marker (lacZ) for neovascularization
Developmental Biology Research
Genetics Research
      Tissue/Cell Markers: endothelial cells

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Flt1tm1Jrt
Allele Name targeted mutation 1, Janet Rossant
Allele Type Targeted (Null/Knockout, Reporter)
Common Name(s) Flt-1-; Flt-1lacZ; Flt1lacZ; VEGFR1-lacZ; flt-1lcz;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Flt1, FMS-like tyrosine kinase 1
Chromosome 5
Gene Common Name(s) AI323757; FLT; FLT-1; Flt-1; VEGFR-1; VEGFR1; expressed sequence AI323757; sFlt1; vascular endothelial growth factor receptor-1;
Molecular Note A LacZ-neomycin resistance cassette replaced sequences that encode the signal peptide. The authors predict this is a null allele because the translation start site is removed and reinitiation at the first two downstream Kozak sequences would result in out-of-frame translated products. [MGI Ref ID J:26845]

Genotyping

Genotyping Information

Genotyping Protocols

Generic LacZ Melt Curve Analysis, Melt Curve Analysis


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fong GH; Rossant J; Gertsenstein M; Breitman ML. 1995. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376(6535):66-70. [PubMed: 7596436]  [MGI Ref ID J:26845]

Additional References

Flt1tm1Jrt related

Addya S; Shiroto K; Turoczi T; Zhan L; Kaga S; Fukuda S; Surrey S; Duan LJ; Fong GH; Yamamoto F; Maulik N. 2005. Ischemic preconditioning-mediated cardioprotection is disrupted in heterozygous Flt-1 (VEGFR-1) knockout mice. J Mol Cell Cardiol 38(2):345-51. [PubMed: 15698841]  [MGI Ref ID J:101949]

Chappell JC; Taylor SM; Ferrara N; Bautch VL. 2009. Local guidance of emerging vessel sprouts requires soluble Flt-1. Dev Cell 17(3):377-86. [PubMed: 19758562]  [MGI Ref ID J:152835]

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 Ref ID 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 Ref ID 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 Ref ID 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 Ref ID J:129132]

Erskine L; Reijntjes S; Pratt T; Denti L; Schwarz Q; Vieira JM; Alakakone B; Shewan D; Ruhrberg C. 2011. VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron 70(5):951-65. [PubMed: 21658587]  [MGI Ref ID J:174966]

Fong GH; Klingensmith J; Wood CR; Rossant J; Breitman ML. 1996. Regulation of flt-1 expression during mouse embryogenesis suggests a role in the establishment of vascular endothelium. Dev Dyn 207(1):1-10. [PubMed: 8875071]  [MGI Ref ID J:35177]

Fong GH; Zhang L; Bryce DM; Peng J. 1999. Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development 126(13):3015-25. [PubMed: 10357944]  [MGI Ref ID J:54830]

Hirashima M; Lu Y; Byers L; Rossant J. 2003. Trophoblast expression of fms-like tyrosine kinase 1 is not required for the establishment of the maternal-fetal interface in the mouse placenta. Proc Natl Acad Sci U S A 100(26):15637-42. [PubMed: 14668430]  [MGI Ref ID J:88147]

Ho VC; Duan LJ; Cronin C; Liang BT; Fong GH. 2012. Elevated vascular endothelial growth factor receptor-2 abundance contributes to increased angiogenesis in vascular endothelial growth factor receptor-1-deficient mice. Circulation 126(6):741-52. [PubMed: 22753193]  [MGI Ref ID J:202202]

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]

Kappas NC; Zeng G; Chappell JC; Kearney JB; Hazarika S; Kallianos KG; Patterson C; Annex BH; Bautch VL. 2008. The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching. J Cell Biol 181(5):847-58. [PubMed: 18504303]  [MGI Ref ID J:137022]

Kearney JB; Ambler CA; Monaco KA; Johnson N; Rapoport RG; Bautch VL. 2002. Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood 99(7):2397-407. [PubMed: 11895772]  [MGI Ref ID J:75836]

Kearney JB; Kappas NC; Ellerstrom C; DiPaola FW; Bautch VL. 2004. The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood 103(12):4527-35. [PubMed: 14982871]  [MGI Ref ID J:90967]

Murakami M; Zheng Y; Hirashima M; Suda T; Morita Y; Ooehara J; Ema H; Fong GH; Shibuya M. 2008. VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arterioscler Thromb Vasc Biol 28(4):658-64. [PubMed: 18174461]  [MGI Ref ID J:149043]

Nishi J; Minamino T; Miyauchi H; Nojima A; Tateno K; Okada S; Orimo M; Moriya J; Fong GH; Sunagawa K; Shibuya M; Komuro I. 2008. Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt. Circ Res 103(3):261-8. [PubMed: 18583712]  [MGI Ref ID J:151369]

Pennisi D; Gardner J; Chambers D; Hosking B; Peters J; Muscat G; Abbott C; Koopman P. 2000. Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice. Nat Genet 24(4):434-7. [PubMed: 10742113]  [MGI Ref ID J:61488]

Sano K; Katsuta O; Shirae S; Kubota Y; Ema M; Suda T; Nakamura M; Hirashima M. 2012. Flt1 and Flk1 mediate regulation of intraocular pressure and their double heterozygosity causes the buphthalmia in mice. Biochem Biophys Res Commun 420(2):422-7. [PubMed: 22426483]  [MGI Ref ID J:183383]

Storkebaum E; Ruiz de Almodovar C; Meens M; Zacchigna S; Mazzone M; Vanhoutte G; Vinckier S; Miskiewicz K; Poesen K; Lambrechts D; Janssen GM; Fazzi GE; Verstreken P; Haigh J; Schiffers PM; Rohrer H; Van der Linden A; De Mey JG; Carmeliet P. 2010. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation 122(3):273-81. [PubMed: 20606119]  [MGI Ref ID J:178592]

Thirunavukkarasu M; Juhasz B; Zhan L; Menon VP; Tosaki A; Otani H; Maulik N. 2007. VEGFR1 (Flt-1+/-) gene knockout leads to the disruption of VEGF-mediated signaling through the nitric oxide/heme oxygenase pathway in ischemic preconditioned myocardium. Free Radic Biol Med 42(10):1487-95. [PubMed: 17448895]  [MGI Ref ID J:121615]

Verma M; Asakura Y; Hirai H; Watanabe S; Tastad C; Fong GH; Ema M; Call JA; Lowe DA; Asakura A. 2010. Flt-1 haploinsufficiency ameliorates muscular dystrophy phenotype by developmentally increased vasculature in mdx mice. Hum Mol Genet 19(21):4145-59. [PubMed: 20705734]  [MGI Ref ID J:164891]

Wada T; Haigh JJ; Ema M; Hitoshi S; Chaddah R; Rossant J; Nagy A; van der Kooy D. 2006. Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. J Neurosci 26(25):6803-12. [PubMed: 16793887]  [MGI Ref ID J:109983]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as heterozygotes. Homozygous mice have an embryonic lethal phenotype, failing to develop past embryonic days 8.5.
Mating SystemWild-type x Heterozygote         (Female x Male)   06-MAR-14
Heterozygote x Wild-type         (Female x Male)   06-MAR-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 29-DEC-14

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Flt1tm1Jrt  
Price per Pair (US dollars $)Pair Genotype
$304.00Heterozygous for Flt1tm1Jrt x Wild-type for Flt1tm1Jrt  
$304.00Wild-type for Flt1tm1Jrt x Heterozygous for Flt1tm1Jrt  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Flt1tm1Jrt  
Price per Pair (US dollars $)Pair Genotype
$395.20Heterozygous for Flt1tm1Jrt x Wild-type for Flt1tm1Jrt  
$395.20Wild-type for Flt1tm1Jrt x Heterozygous for Flt1tm1Jrt  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

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

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


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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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