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Strain Name:

FVB-Tg(tetO/CMV-KRAS*G12C)9.1Msmi/J

Stock Number:

006439

Availability:

Repository- Live

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Genes & Alleles   KRAS;   CMV;   Tg(tetO/CMV-KRAS*G12C)9.1Msmi;   tetO;

Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Mating System+/+ sibling x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Mark Miller,   Wake Forest Univ, School of Medicine
Generation+N1F1 (21-MAY-07)

Strain Description
Hemizygous mice are viable and fertile. These 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.

Strain 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.

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)

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

Gene & Allele Details

Allele Symbol Tg(tetO/CMV-KRAS*G12C)9.1Msmi
Allele Name transgene insertion 9.1, Mark Miller
Common Name(s) Ki-rasG12C;
Mutation Made By Mark Miller,   Wake Forest Univ, School of Medicine
Strain of OriginFVB/NTac
Expressed Gene KRAS, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, human
Promoter CMV, cytomegalovirus, human
Promoter tetO, tet operator,
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]

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(tetO/CMV-KRAS*G12C)9.1Msmi

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

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
004375   FVB/N-Tg(tetO-Kras2)12Hev/J
002471   STOCK Tg(hCMV-cre)140Sau/J
View Strains carrying other alleles of CMV     (5 strains)

View Strains carrying other alleles of tetO     (28 strains)

Additional Web Information

Tet Expression Systems

Animal Health Reports

Room Number           AX11

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)

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

Price and Supply Information

Strain Name: FVB-Tg(tetO/CMV-KRAS*G12C)9.1Msmi/J
Stock Number: 006439

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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

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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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