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| These Ki-rasG12C transgenic mice express the human KRASG12C mutation under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters, transgene expression in the appropriate tissues of the bitransgenic offspring can be regulated with the tetracycline analog, doxycycline. | |||||||||||||||
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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
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +N1F1pN1 Donating Investigator Mark Miller, Wake Forest Univ, School of Medicine Description
Hemizygous mice are viable and fertile. These Ki-rasG12C transgenic mice express the human KRASG12C mutation under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters, transgene expression in the appropriate tissues of the bitransgenic offspring can be regulated with the tetracycline analog, doxycycline.When crossed with mice containing a lung-specific tTA protein (e.g. Stock Nos. 006222, 006232, 006242 or 006225), treatment with doxycycline results in the formation of benign hyperplastic lesions starting at 12 weeks and the development of benign adenomas by 6 months. Tumors do not progress in size, but multiplicity increases upon further treatment with doxycyline. These bitransgenic mice live for at least 12 months and show a benign phenotype as compared with other mutant KRAS transgenic strains (e.g. Stock No. 004375), which demonstrate more aggressive tumor phenotypes. Doxycycline withdrawl from the diet of bitransgenic mice results in tumor regression.
Development
A genomic segment including the KRASG12C (Ki-rasG12C) mutation was cloned from the H358 human lung bronchioalveolar cell line and placed under the regulation of a tetracycline-responsive element (TRE; tetO). The transgenic construct was microinjected into fertilized FVB/N mouse eggs. Transgenic founders were crossed with non-transgenic littermates to establish germline transmission.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of CMV
006054 B6.C-Tg(CMV-cre)1Cgn/J 008301 B6.Cg-Tg(CMV-Klc1)90Gsn/J 007237 B6.Cg-Tg(CMV-Serpine1)1Dgi/J 003465 BALB/c-Tg(CMV-cre)1Cgn/J 006362 C57BL/6J-Tg(CMV-Cox8a/EYFP)17J/J 008450 FVB-Tg(CAG-luc,-GFP)L2G85Chco/J 004375 FVB/N-Tg(tetO-Kras2)12Hev/J 002471 STOCK Tg(hCMV-cre)140Sau/J View Strains carrying other alleles of CMV (8 strains)
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO/CMV-KRAS*G12C)9.1Msmi/0
involves: FVB/N
- respiratory system phenotype
- abnormal lung morphology (MGI Ref ID J:102839)
- after 12 days of doxycycline (DOX) treatement, small, hyperplastic lung foci are detected; untreated mice have normal lungs
- abnormal respiratory alveolar epithelial cell morphology (MGI Ref ID J:102839)
- after 5 weeks of DOX treatment, extensive epithelial hyperplasia of alveolar region of lung is observed; untreated mice have normal lungs
- abnormal respiratory system physiology (MGI Ref ID J:102839)
- abnormal surfactant physiology (MGI Ref ID J:102839)
- alveolar lipoproteinosis is regularly found, indicating abnormal surfactant metabolism
- tumorigenesis
- increased tumor incidence (MGI Ref ID J:102839)
- after 3 months treatment, visible macroscopic lesions are found; tumor incidence at 3 months is 55%, with multiplicity of 1.7 tumors/mouse
- lesions are <1mm in size
- early hyperplastic lesions are of alveologenic origin
- at 6 and 9 months DOX treatment, visible lesions increase in number; multiplicity is 10.2 and 12.5 tumors/mouse after 9 and 12 months, lower than Scgb1a1/KRAS bitransgenic mice; treated monotransgenic mice show no incidence
- when DOX treatment was stopped after 9 months, within 2 weeks only 4 tumors are visible on lung surface and by 1 month, no tumors are visible, and with minimal hyperplastic foci microscopically detectable, showing no proliferation (or apoptosis)
- lung adenoma (MGI Ref ID J:102839)
Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO/CMV-KRAS*G12C)9.1Msmi/0
involves: FVB/N
- respiratory system phenotype
- abnormal lung morphology (MGI Ref ID J:102839)
- after 12 days of doxycycline (DOX) treatement, small, hyperplastic lung foci are detected; untreated mice have normal lungs
- abnormal respiratory alveolar epithelial cell morphology (MGI Ref ID J:102839)
- after 5 weeks of DOX treatment, extensive epithelial hyperplasia of alveolar region of lung is observed; untreated mice have normal lungs
- tumorigenesis
- increased tumor incidence (MGI Ref ID J:102839)
- after 3 months treatment, visible macroscopic lesions are found; tumor incidence at 3 months is 55%, with multiplicity of 3.5 tumors/mouse
- lesions are <1mm in size
- early hyperplastic lesions are of bronchiolar origin
- at 6 and 9 months DOX treatment, visible lesions increase in number; multiplicity is 28.8 and 34 tumors/mouse after 9 and 12 months, higher than SFTPC/KRAS bitransgenic mice; treated monotransgenic mice show no tumor incidence
- when DOX treatment was stopped after 9 months, within 2 weeks only 4 tumors are visible on lung surface; these remain after 1 months; minimal hyperplastic foci microscopically are detectable, showing no proliferation (or apoptosis)
- lung adenocarcinoma (MGI Ref ID J:102839)
- at 12 months of treatment, 2 adenomas have progressed to low grade carcinomas
- lung adenoma (MGI Ref ID J:102839)
- single adenoma was detected at 3 months; at 6, 9, and 12 months of treatment, incidence increases; mice develop higher incidence of proliferative changes with lower latency than SFTPC/KRAS mice
This mouse can be used to support research in many areas including:
Cancer Research
Increased Tumor Incidence
Adenomas: lung, induced
Other Tissues/Organs: lung, induced
Research Tools
Tet Expression Systems
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(tetO/CMV-KRAS*G12C)9.1Msmi | ||
|---|---|---|---|
| Allele Name | transgene insertion 9.1, Mark Miller | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Ki-rasG12C; | ||
| Mutation Made By | Mark Miller, Wake Forest Univ, School of Medicine | ||
| Strain of Origin | FVB/NTac | ||
| Expressed Gene | KRAS, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, human | ||
| Promoter | tetO, tet operator, | ||
| Promoter | CMV, cytomegalovirus, human | ||
| Molecular Note | A genomic segment including the KRASG12C mutation was cloned from the H358 human lung bronchioalveolar cell line and placed under the regulation of a tetracycline-inducible (tetO)/cytomegalovirus (CMV) promoter. Copy number is estimated at 22. [MGI Ref ID J:102839] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(tetO/CMV-KRAS*G12C)9.1Msmi, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Floyd HS; Farnsworth CL; Kock ND; Mizesko MC; Little JL; Dance ST; Everitt J; Tichelaar J; Whitsett JA; Miller MS. 2005. Conditional expression of the mutant Ki-rasG12C allele results in formation of benign lung adenomas: development of a novel mouse lung tumor model. Carcinogenesis 26(12):2196-206. [PubMed: 16051643] [MGI Ref ID J:102839]
Additional References
Tg(tetO/CMV-KRAS*G12C)9.1Msmi relatedDance-Barnes ST; Kock ND; Floyd HS; Moore JE; Mosley LJ; D'Agostino RB Jr; Pettenati MJ; Miller MS. 2008. Effects of mutant human Ki-ras(G12C) gene dosage on murine lung tumorigenesis and signaling to its downstream effectors. Toxicol Appl Pharmacol 231(1):77-84. [PubMed: 18565564] [MGI Ref ID J:139881]
Dance-Barnes ST; Kock ND; Moore JE; Lin EY; Mosley LJ; D'Agostino RB Jr; McCoy TP; Townsend AJ; Miller MS. 2009. Lung tumor promotion by curcumin. Carcinogenesis 30(6):1016-23. [PubMed: 19359593] [MGI Ref ID J:149324]
Floyd HS; Jennings-Gee JE; Kock ND; Miller MS. 2006. Genetic and epigenetic alterations in lung tumors from bitransgenic Ki-rasG12C expressing mice. Mol Carcinog 45(7):506-17. [PubMed: 16482519] [MGI Ref ID J:110395]
Health & husbandry
Health & Colony Maintenance Information
Currently there no information available for this strain. This may be due to the supply level of this strain.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
Additional Supply Details
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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.
Additional Supply Details
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Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 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. | ||
Payment Terms and Conditions
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.
See Terms of Use tab for General Terms and Conditions
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.Ordering and Purchasing Information
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Use of the Tet-System may require a license, see Licenses for Strains Using TET-System Technology.
For additional Licensing and Use Restrictions view the link(s) below:
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| fax: | 207-288-6655 |
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