Strain Name:

FVB/N-Tg(tetO-Kras2)12Hev/J

Stock Number:

004375

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Availability:

Cryopreserved - Ready for recovery

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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

Former Names FVB/N-Tg(teto-Kras2)12Hev    (Changed: 15-DEC-04 )
Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Harold E. Varmus,   Memorial Sloan-Kettering Cancer Center

Description
Mice that are homozygous for the transgene are viable and fertile. These transgenic mice express activated rat Kras (Kras4bG12D) under the regulation of a tetracycline-responsive promoter element (TRE; tetO). When these mice are mated to strains containing transgenes encoding either rtTA (reverse tetracycline trans-activator protein) or tTA (the tetracycline trans-activator), activated Kras expression in the bitransgenic animals can be induced by administration or withdrawl, respectively, of the tetracycline analog, doxycycline. This strain represents an effective tool for generating tissue specific mutants that would be useful models for studying oncogene activation in human carcinogenesis.

Development
A transgenic construct containing the mutant gene (Kras4bG12D) under the regulation of a tetracycline-responsive promoter element (TRE; tetO), the mp-1 intron and polyadenylation site sequence, and a minimal CMV promoter was injected into FVB/N blastocysts.

Control Information

  Control
   001800 FVB/NJ
 
  Considerations for Choosing Controls

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View Strains carrying other alleles of CMV     (36 strains)

Phenotype

Phenotype Information

View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Adenomas
      Adenomas: lung, induced
      Other Tissues/Organs
      Other Tissues/Organs: lung, induced

Research Tools
Tet Expression Systems
      tTA/rtTA Responsive Strains

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(tetO-Kras2)12Hev
Allele Name transgene insertion 12, Harold E Varmus
Allele Type Transgenic (random, expressed)
Common Name(s) K-Ras4bG12D responder; K-Ras4bG12D responder; K-ras4bG12D; K-rasG12D-5; KE; TOR; TRE-KrasG12D; Tet-op-K-RasG12D; Tet-op-K-ras; TetO-KrasG12D; tre-Kras;
Mutation Made ByDr. Harold Varmus,   Memorial Sloan-Kettering Cancer Center
Strain of OriginFVB/N
Expressed Gene Kras, Kirsten rat sarcoma viral oncogene, rat
Promoter CMV, cytomegalovirus, human
General Note Homozygous transgenic mice are viable and fertile. In conjunction with a second transgene encoding either rtTA (reverse tetracycline trans-activator protein) or tTA (the tetracycline trans-activator), mice carrying Tg(tetO-Kras2)12Hev show tissue-specific expression of the mutated K-ras transgene that may be induced or suppressed by administration of the tetracycline analog, doxycycline. Cessation or initiation of doxycycline treatment in bitransgenic strains containing, respectively, rtTA or tTA, will result in a rapid decrease of expression of the transgene.
Molecular Note The transgene expresses the mutant gene Kras4bG12D, under the control of a tetracycline-responsive promoter element (tTA), mp-1 intron polyadenylation site sequence, and a minimal CMV promoter. [MGI Ref ID J:73468]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(tetO-Kras2)12Hev, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fisher GH; Wellen SL; Klimstra D; Lenczowski JM; Tichelaar JW; Lizak MJ; Whitsett JA; Koretsky A; Varmus HE. 2001. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev 15(24):3249-62. [PubMed: 11751631]  [MGI Ref ID J:73468]

Additional References

Tg(tetO-Kras2)12Hev related

Chow HY; Jubb AM; Koch JN; Jaffer ZM; Stepanova D; Campbell DA; Duron SG; O'Farrell M; Cai KQ; Klein-Szanto AJ; Gutkind JS; Hoeflich KP; Chernoff J. 2012. p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model. Cancer Res 72(22):5966-75. [PubMed: 22983922]  [MGI Ref ID J:192901]

Collins MA; Bednar F; Zhang Y; Brisset JC; Galban S; Galban CJ; Rakshit S; Flannagan KS; Adsay NV; Pasca di Magliano M. 2012. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest 122(2):639-53. [PubMed: 22232209]  [MGI Ref ID J:184378]

Collins MA; Brisset JC; Zhang Y; Bednar F; Pierre J; Heist KA; Galban CJ; Galban S; di Magliano MP. 2012. Metastatic pancreatic cancer is dependent on oncogenic Kras in mice. PLoS One 7(12):e49707. [PubMed: 23226501]  [MGI Ref ID J:195686]

Duran A; Linares JF; Galvez AS; Wikenheiser K; Flores JM; Diaz-Meco MT; Moscat J. 2008. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 13(4):343-54. [PubMed: 18394557]  [MGI Ref ID J:136133]

Engelman JA; Chen L; Tan X; Crosby K; Guimaraes AR; Upadhyay R; Maira M; McNamara K; Perera SA; Song Y; Chirieac LR; Kaur R; Lightbown A; Simendinger J; Li T; Padera RF; Garcia-Echeverria C; Weissleder R; Mahmood U; Cantley LC; Wong KK. 2008. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 14(12):1351-6. [PubMed: 19029981]  [MGI Ref ID J:142254]

Galvez AS; Duran A; Linares JF; Pathrose P; Castilla EA; Abu-Baker S; Leitges M; Diaz-Meco MT; Moscat J. 2009. Protein kinase Czeta represses the interleukin-6 promoter and impairs tumorigenesis in vivo. Mol Cell Biol 29(1):104-15. [PubMed: 18955501]  [MGI Ref ID J:144073]

Hsu TI; Wang MC; Chen SY; Yeh YM; Su WC; Chang WC; Hung JJ. 2012. Sp1 expression regulates lung tumor progression. Oncogene 31(35):3973-88. [PubMed: 22158040]  [MGI Ref ID J:187868]

Ji H; Wang Z; Perera SA; Li D; Liang MC; Zaghlul S; McNamara K; Chen L; Albert M; Sun Y; Al-Hashem R; Chirieac LR; Padera R; Bronson RT; Thomas RK; Garraway LA; Janne PA; Johnson BE; Chin L; Wong KK. 2007. Mutations in BRAF and KRAS converge on activation of the mitogen-activated protein kinase pathway in lung cancer mouse models. Cancer Res 67(10):4933-9. [PubMed: 17510423]  [MGI Ref ID J:121738]

Kim CF; Jackson EL; Kirsch DG; Grimm J; Shaw AT; Lane K; Kissil J; Olive KP; Sweet-Cordero A; Weissleder R; Jacks T. 2005. Mouse models of human non-small-cell lung cancer: raising the bar. Cold Spring Harb Symp Quant Biol 70:241-50. [PubMed: 16869760]  [MGI Ref ID J:116813]

Konstantinidou G; Bey EA; Rabellino A; Schuster K; Maira MS; Gazdar AF; Amici A; Boothman DA; Scaglioni PP. 2009. Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations. Cancer Res 69(19):7644-52. [PubMed: 19789349]  [MGI Ref ID J:153586]

Konstantinidou G; Ramadori G; Torti F; Kangasniemi K; Ramirez RE; Cai Y; Behrens C; Dellinger MT; Brekken RA; Wistuba II; Heguy A; Teruya-Feldstein J; Scaglioni PP. 2013. RHOA-FAK is a required signaling axis for the maintenance of KRAS-driven lung adenocarcinomas. Cancer Discov 3(4):444-57. [PubMed: 23358651]  [MGI Ref ID J:198243]

Munoz DM; Singh S; Tung T; Agnihotri S; Nagy A; Guha A; Zadeh G; Hawkins C. 2013. Differential transformation capacity of neuro-glial progenitors during development. Proc Natl Acad Sci U S A 110(35):14378-83. [PubMed: 23942126]  [MGI Ref ID J:200905]

Nielsen CH; Kimura RH; Withofs N; Tran PT; Miao Z; Cochran JR; Cheng Z; Felsher D; Kjaer A; Willmann JK; Gambhir SS. 2010. PET imaging of tumor neovascularization in a transgenic mouse model with a novel 64Cu-DOTA-knottin peptide. Cancer Res 70(22):9022-30. [PubMed: 21062977]  [MGI Ref ID J:166856]

Podsypanina K; Politi K; Beverly LJ; Varmus HE. 2008. Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proc Natl Acad Sci U S A 105(13):5242-7. [PubMed: 18356293]  [MGI Ref ID J:133578]

Politi K; Fan PD; Shen R; Zakowski M; Varmus H. 2010. Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma. Dis Model Mech 3(1-2):111-9. [PubMed: 20007486]  [MGI Ref ID J:157671]

Raimondi AR; Vitale-Cross L; Amornphimoltham P; Gutkind JS; Molinolo A. 2006. Rapid development of salivary gland carcinomas upon conditional expression of K-ras driven by the cytokeratin 5 promoter. Am J Pathol 168(5):1654-65. [PubMed: 16651631]  [MGI Ref ID J:108579]

Redente EF; Dwyer-Nield LD; Merrick DT; Raina K; Agarwal R; Pao W; Rice PL; Shroyer KR; Malkinson AM. 2010. Tumor progression stage and anatomical site regulate tumor-associated macrophage and bone marrow-derived monocyte polarization. Am J Pathol 176(6):2972-85. [PubMed: 20431028]  [MGI Ref ID J:161329]

Sotillo R; Schvartzman JM; Socci ND; Benezra R. 2010. Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature 464(7287):436-40. [PubMed: 20173739]  [MGI Ref ID J:158125]

Sullivan JP; Spinola M; Dodge M; Raso MG; Behrens C; Gao B; Schuster K; Shao C; Larsen JE; Sullivan LA; Honorio S; Xie Y; Scaglioni PP; DiMaio JM; Gazdar AF; Shay JW; Wistuba II; Minna JD. 2010. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res 70(23):9937-48. [PubMed: 21118965]  [MGI Ref ID J:166963]

Tilli MT; Furth PA. 2003. Conditional mouse models demonstrate oncogene-dependent differences in tumor maintenance and recurrence. Breast Cancer Res 5(4):202-5. [PubMed: 12817992]  [MGI Ref ID J:84503]

Tran PT; Bendapudi PK; Lin HJ; Choi P; Koh S; Chen J; Horng G; Hughes NP; Schwartz LH; Miller VA; Kawashima T; Kitamura T; Paik D; Felsher DW. 2011. Survival and death signals can predict tumor response to therapy after oncogene inactivation. Sci Transl Med 3(103):103ra99. [PubMed: 21974937]  [MGI Ref ID J:178317]

Tran PT; Shroff EH; Burns TF; Thiyagarajan S; Das ST; Zabuawala T; Chen J; Cho YJ; Luong R; Tamayo P; Salih T; Aziz K; Adam SJ; Vicent S; Nielsen CH; Withofs N; Sweet-Cordero A; Gambhir SS; Rudin CM; Felsher DW. 2012. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant kras-induced lung tumorigenesis. PLoS Genet 8(5):e1002650. [PubMed: 22654667]  [MGI Ref ID J:185196]

Tran TP; Fan AC; Bendapudi PK; Koh S; Komatsubara K; Chen J; Horng G; Bellovin DI; Giuriato S; Wang CS; Whitsett JA; Felsher DW. 2008. Combined Inactivation of MYC and K-Ras oncogenes reverses tumorigenesis in lung adenocarcinomas and lymphomas. PLoS ONE 3(5):e2125. [PubMed: 18461184]  [MGI Ref ID J:136212]

Varmus H; Pao W; Politi K; Podsypanina K; Du YC. 2005. Oncogenes come of age. Cold Spring Harb Symp Quant Biol 70:1-9. [PubMed: 16869733]  [MGI Ref ID J:116747]

Vitale-Cross L; Amornphimoltham P; Fisher G; Molinolo AA; Gutkind JS. 2004. Conditional expression of K-ras in an epithelial compartment that includes the stem cells is sufficient to promote squamous cell carcinogenesis. Cancer Res 64(24):8804-7. [PubMed: 15604235]  [MGI Ref ID J:94955]

Wang IC; Snyder J; Zhang Y; Lander J; Nakafuku Y; Lin J; Chen G; Kalin TV; Whitsett JA; Kalinichenko VV. 2012. Foxm1 mediates cross talk between Kras/mitogen-activated protein kinase and canonical Wnt pathways during development of respiratory epithelium. Mol Cell Biol 32(19):3838-50. [PubMed: 22826436]  [MGI Ref ID J:188926]

Zeng X; Shaikh FY; Harrison MK; Adon AM; Trimboli AJ; Carroll KA; Sharma N; Timmers C; Chodosh LA; Leone G; Saavedra HI. 2010. The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2. Oncogene 29(36):5103-12. [PubMed: 20581865]  [MGI Ref ID J:169196]

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 FVB/N background and has been maintained on the same.

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* $2450.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

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 11 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* $3185.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

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 11 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
   001800 FVB/NJ
 
  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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