Strain Name:

B6.129S2-F5tm2Dgi/J

Stock Number:

004080

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These F5 Leiden mutation mice serve as a model for blood coagulation defects.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator David Ginsburg,   University of Michigan

Description
These mice carry the F5 Leiden mutation whereby the arginine at position 504 is replaced by a glutamine disrupting a cleavage site necessary for the inactivation of the factor V protein. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Clotting activity is indistinguishable from that of wildtype mice. Rarely, spontaneous vascular thrombo-embolic events are observed. Analysis of tissue fibrin content indicates increased deposition of fibrin in multiple tissues. When maintained on a mixed B6;129 genetic background, mice homozygous for this allele experience disseminated intravascular thrombosis resulting in increased fetal loss. This loss is not observed on a congenic C57BL/6J genetic background. This mutant mouse strain represents a model useful in research examining the disease aspects of the Leiden mutation and thrombosis in general.

Development
A targeting vector containing F5 exons 7-11, with a TK/neo cassette flanked by loxP sites located in intron 10 and a point mutation in exon 10 (mutation R504Q) was introduced into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with supercoiled pMC-Cre plasmid DNA to remove the TK/neo cassette. ES cells bearing the R504Q mutation and bereft of the TK/Neo cassette were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females. Mutant mice were then backcrossed to C57BL/6J for twelve generations before being made homozygous.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of F5
004078   B6.129S2-F5tm1Dgi/J
007244   B6;SJL-Tg(Alb-F5)2Dgi/J
007245   B6;SJL-Tg(Alb-F5)3Dgi/J
007243   B6;SJL-Tg(Cxcl4-F5)1Dgi/J
View Strains carrying other alleles of F5     (4 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.
Budd-Chiari Syndrome; BDCHS   (F5)
Factor V Deficiency   (F5)
Pregnancy Loss, Recurrent, Susceptibility to, 1; RPRGL1   (F5)
Stroke, Ischemic   (F5)
Thrombophilia Due to Activated Protein C Resistance; THPH2   (F5)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

F5tm2Dgi/F5+

        B6.129S2-F5tm2Dgi
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • more resistant to anticoagulant activated protein C than controls, however F5 clotting activity is normal   (MGI Ref ID J:66260)
    • thrombosis
      • exhibit occasional spontaneous vascular thrombosis (e.g. necrosis of a digit)   (MGI Ref ID J:66260)

F5tm2Dgi/F5tm2Dgi

        B6.129S2-F5tm2Dgi
  • mortality/aging
  • *normal* mortality/aging
    • do not observe postnatal lethality on the predominately C57BL/6J background like on the mixed 129 and C57BL/6J background, however crossing back to 129/SvJ or 129SvIm/J mice, results in about 50% postnatal loss   (MGI Ref ID J:66260)
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • chronic, low-grade thrombin generation leading to enhanced fibrin deposition in multiple tissues, however do not observe thrombosis   (MGI Ref ID J:66260)
  • liver fibrosis
    • occasional focal hepatic fibrosis is seen   (MGI Ref ID J:66260)
  • liver/biliary system phenotype
  • liver fibrosis
    • occasional focal hepatic fibrosis is seen   (MGI Ref ID J:66260)

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

F5tm2Dgi/F5tm2Dgi

        involves: 129S2/SvPas * C57BL/6J
  • mortality/aging
  • *normal* mortality/aging
    • decreased number of expected pups at 3 weeks of age but not at 1-2 days before birth, however do not observe lethality on a predominately C57BL/6J background   (MGI Ref ID J:66260)
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation
    • more resistant to anticoagulant activated protein C than controls or heterozygotes, however F5 clotting activity is normal   (MGI Ref ID J:66260)
    • thrombosis
      • widespread thrombosis affecting multiple organs, including brain, liver, heart, pancreas, and spleen, in all newborns   (MGI Ref ID J:66260)
  • behavior/neurological phenotype
  • lethargy
    • subset of mice appear lethargic at birth   (MGI Ref ID J:66260)
  • integument phenotype
  • pallor
    • subset of mice appear pale at birth   (MGI Ref ID J:66260)

F5tm2Dgi/F5tm2Dgi

        involves: 129S2/SvPas * C57BL/6
  • mortality/aging
  • partial neonatal lethality
    • around 20% of homozygotes die in neonatal period   (MGI Ref ID J:62716)
  • homeostasis/metabolism phenotype
  • thrombosis
    • homozygotes that die show microvascular thrombosis in neonatal period   (MGI Ref ID J:62716)
View Research Applications

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

F5tm2Dgi related

Hematological Research
Clotting Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol F5tm2Dgi
Allele Name targeted mutation 2, David Ginsburg
Allele Type Targeted
Common Name(s) FVLeiden; FVLq; FvQ; FvL; FvR504Q;
Mutation Made By Jisong Cui,   University of Michigan
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Promoter F5, coagulation factor V, mouse, laboratory
Molecular Note A point mutation was introduced which altered the codon corresponding to amino acid 504 from an arginine to a glutamine. A loxP flanked neomycin cassette in intron 10 was removed by Cre-mediated recombination in ES cells prior to blastocyst injection. [MGI Ref ID J:66260]

Genotyping

Genotyping Information

Genotyping Protocols

F5tm2Dgi, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

F5tm2Dgi related

An J; Waitara MS; Bordas M; Arumugam V; Hoffmann RG; Petrich BG; Sinha U; North PE; Sood R. 2013. Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model. Blood 121(11):2127-34. [PubMed: 23325830]  [MGI Ref ID J:195883]

Cui J; Eitzman DT; Westrick RJ; Christie PD; Xu ZJ; Yang AY; Purkayastha AA; Yang TL; Metz AL; Gallagher KP; Tyson JA; Rosenberg RD; Ginsburg D. 2000. Spontaneous thrombosis in mice carrying the factor V leiden mutation Blood 96(13):4222-6. [PubMed: 11110695]  [MGI Ref ID J:66260]

Eitzman DT; Westrick RJ; Shen Y; Bodary PF; Gu S; Manning SL; Dobies SL; Ginsburg D. 2005. Homozygosity for factor V Leiden leads to enhanced thrombosis and atherosclerosis in mice. Circulation 111(14):1822-5. [PubMed: 15809370]  [MGI Ref ID J:109686]

Kisucka J; Chauhan AK; Zhao BQ; Patten IS; Yesilaltay A; Krieger M; Wagner DD. 2009. Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood 113(23):6015-22. [PubMed: 19349621]  [MGI Ref ID J:149496]

Parker AC; Mundada LV; Schmaier AH; Fay WP. 2004. Factor VLeiden inhibits fibrinolysis in vivo. Circulation 110(23):3594-8. [PubMed: 15569834]  [MGI Ref ID J:103734]

Seehaus S; Shahzad K; Kashif M; Vinnikov IA; Schiller M; Wang H; Madhusudhan T; Eckstein V; Bierhaus A; Bea F; Blessing E; Weiler H; Frommhold D; Nawroth PP; Isermann B. 2009. Hypercoagulability inhibits monocyte transendothelial migration through protease-activated receptor-1-, phospholipase-Cbeta-, phosphoinositide 3-kinase-, and nitric oxide-dependent signaling in monocytes and promotes plaque stability. Circulation 120(9):774-84. [PubMed: 19687358]  [MGI Ref ID J:167110]

Shen Y; Bodary PF; Vargas FB; Homeister JW; Gordon D; Ostenso KA; Shayman JA; Eitzman DT. 2006. Alpha-galactosidase A deficiency leads to increased tissue fibrin deposition and thrombosis in mice homozygous for the factor V Leiden mutation. Stroke 37(4):1106-8. [PubMed: 16514103]  [MGI Ref ID J:135765]

Sood R; Zogg M; Westrick RJ; Guo YH; Kerschen EJ; Girardi G; Salmon JE; Coughlin SR; Weiler H. 2007. Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers. J Exp Med 204(5):1049-56. [PubMed: 17438064]  [MGI Ref ID J:125742]

Sun H; Wang X; Degen JL; Ginsburg D. 2009. Reduced thrombin generation increases host susceptibility to group A streptococcal infection. Blood 113(6):1358-64. [PubMed: 19056689]  [MGI Ref ID J:145540]

Wang H; Madhusudhan T; He T; Hummel B; Schmidt S; Vinnikov IA; Shahzad K; Kashif M; Muller-Krebs S; Schwenger V; Bierhaus A; Rudofsky G; Nawroth PP; Isermann B. 2011. Low but sustained coagulation activation ameliorates glucose-induced podocyte apoptosis: protective effect of factor V Leiden in diabetic nephropathy. Blood 117(19):5231-42. [PubMed: 21389321]  [MGI Ref ID J:173276]

Yin ZF; Huang ZF; Cui J; Fiehler R; Lasky N; Ginsburg D; Broze GJ Jr. 2000. Prothrombotic phenotype of protein Z deficiency. Proc Natl Acad Sci U S A 97(12):6734-8. [PubMed: 10829076]  [MGI Ref ID J:62716]

Zhang J; Tu Y; Lu L; Lasky N; Broze GJ Jr. 2008. Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency. Blood 111(10):4973-8. [PubMed: 18344422]  [MGI Ref ID J:136102]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129P background and has been backcrossed to C57BL/6J for twelve generations before being made homozygous.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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