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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. | |||||||||||||||
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 | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
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)
Strains carrying other alleles of tetO
View Strains carrying other alleles of tetO (36 strains)
Tet Expression Systems
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
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
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
Other Tissues/Organs: lung, induced
Research Tools
Tet Expression Systems
tTA/rtTA Responsive Strains
| 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 Protocols
Tg(tetO/CMV-KRAS*G12C)9.1Msmi, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
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]
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]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| 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.
| 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.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| 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. | ||
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