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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. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
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- References
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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
Generation DefinitionsDonating Investigator Mark S. 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 rtTA 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
View Strains carrying other alleles of CMV (36 strains)
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Bladder Cancer (KRAS)
Breast Cancer (KRAS)
Cardiofaciocutaneous Syndrome (KRAS)
Gastric Cancer, Hereditary Diffuse; HDGC (KRAS)
Lung Cancer (KRAS)
Noonan Syndrome 3; NS3 (KRAS)
Pancreatic Cancer (KRAS)
Schimmelpenning-Feuerstein-Mims Syndrome; SFM (KRAS)
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
- after 12 days of doxycycline (DOX) treatement, small, hyperplastic lung foci are detected; untreated mice have normal lungs (MGI Ref ID J:102839)
- abnormal pulmonary alveolus epithelium morphology
- after 5 weeks of DOX treatment, extensive epithelial hyperplasia of alveolar region of lung is observed; untreated mice have normal lungs (MGI Ref ID J:102839)
- abnormal respiratory system physiology (MGI Ref ID J:102839)
- abnormal surfactant physiology
- alveolar lipoproteinosis is regularly found, indicating abnormal surfactant metabolism (MGI Ref ID J:102839)
- tumorigenesis
- increased tumor incidence
- after 3 months treatment, visible macroscopic lesions are found; tumor incidence at 3 months is 55%, with multiplicity of 1.7 tumors/mouse (MGI Ref ID J:102839)
- lesions are <1mm in size (MGI Ref ID J:102839)
- early hyperplastic lesions are of alveologenic origin (MGI Ref ID J:102839)
- 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 (MGI Ref ID J:102839)
- 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) (MGI Ref ID J:102839)
- increased lung adenoma incidence (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
- after 12 days of doxycycline (DOX) treatement, small, hyperplastic lung foci are detected; untreated mice have normal lungs (MGI Ref ID J:102839)
- abnormal pulmonary alveolus epithelium morphology
- after 5 weeks of DOX treatment, extensive epithelial hyperplasia of alveolar region of lung is observed; untreated mice have normal lungs (MGI Ref ID J:102839)
- tumorigenesis
- increased tumor incidence
- after 3 months treatment, visible macroscopic lesions are found; tumor incidence at 3 months is 55%, with multiplicity of 3.5 tumors/mouse (MGI Ref ID J:102839)
- lesions are <1mm in size (MGI Ref ID J:102839)
- early hyperplastic lesions are of bronchiolar origin (MGI Ref ID J:102839)
- 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 (MGI Ref ID J:102839)
- 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) (MGI Ref ID J:102839)
- increased lung adenoma incidence
- 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 (MGI Ref ID J:102839)
- lung adenocarcinoma
- at 12 months of treatment, 2 adenomas have progressed to low grade carcinomas (MGI Ref ID J:102839)
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/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 provided by MGI
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
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2085.00 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.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
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 |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2710.50 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.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
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).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| 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 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 Information
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