Description

Strain Information

Former Names FVB/N-Tg(teto-Kras2)12Hev    (Changed: 15-DEC-04 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F?+2+N1p (07-MAR-04)   Donating Investigator Harold 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 (Kras4b^G12D) 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 (Kras4b^G12D) 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

Related Strains

Strains carrying other alleles of CMV

006054	B6.C-Tg(CMV-cre)1Cgn/J
003465	BALB/c-Tg(CMV-cre)1Cgn/J
006362	C57BL/6J-Tg(CMV-Cox8a/EYFP)17J/J
006439	FVB-Tg(tetO/CMV-KRAS*G12C)9.1Msmi/J
002471	STOCK Tg(hCMV-cre)140Sau/J

View Strains carrying other alleles of CMV     (5 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: lung, induced)
Increased Tumor Incidence (Other Tissues/Organs: lung, induced)

Research Tools
Tet Expression Systems (tTA/rtTA Responsive Strains)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(tetO-Kras2)12Hev
Allele Name		transgene insertion 12, Harold E Varmus
Allele Type		Transgenic (random, expressed)
Common Name(s)		K-Ras4b responder; K-Ras4bG12D responder; K-ras4bG12D; K-rasG12D-5; KE; TOR; Tet-op-K-RasG12D; Tet-op-K-ras; TetO-KrasG12D; tre-Kras;
Mutation Made By		Harold Varmus,   Memorial Sloan-Kettering Cancer Center
Strain of Origin		FVB/N
Expressed Gene		Kras, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, 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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

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]

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]

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]

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]

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 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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a FVB/N background and has been maintained on the same.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	001800 FVB/NJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Use of the Tet-System may require a license, see Licenses for Strains Using TET-System Technology.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.