Overview

Also Known As:KPC, tamoxifen-inducible

This tamoxifen-inducible KPC strain may be used as a model for pancreatic ductal adenocarcinoma (PDAC).

Donating Investigator

The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	N1F4 (2020-02-27 00:00:00)

Trp53^tm1Brn

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Trp53	transformation related protein 53

Kras^tm4Tyj

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Kras	Kirsten rat sarcoma viral oncogene homolog

Allele Type
Transgenic (Recombinase-expressing)

Research Applications

Research Tools
Cancer Research

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female 4-week

View Price List

Details

Detailed Description

This KPC strain is a tamoxifen-inducible model for pancreatic ductal adenocarcinoma (PDAC) carrying the Kras LSL G12D (Kras^tm4Tyj) allele, the Trp53^tm1Brn floxed allele, and the Tg(Pdx1-cre/Esr1*)#Dam transgene. These KPC mice develop acinar-to-ductal metaplasias and pancreatic intraepithelial neoplasias (PanIN) within 8-10 weeks following tamoxifen administration, and invasive pancreatic ductal adenocarcinoma within 14-16 weeks. The time course and metastatic spread (to liver, lung, parietal peritoneum and diaphragm) is similar to the phenotype observed in the KPC model of PDAC. Histological analysis of pancreatic lesions shows the same type of multifocal tumors seen in the KPC model.

The Kras^tm4Tyj allele contains a point mutation (G12D) whose expression is blocked by the presence of a loxP-flanked stop codon. Mice homozygous for the Kras^tm4Tyj allele die in utero. Cre-mediated recombination can excise the stop codon and permit the oncogenic protein to be expressed.

The Trp53^tm1Brn allele contains loxP sites flanking exons 2 through 10 of the Trp53 gene. Mice homozygous for the Trp53^tm1Brn allele have a somewhat reduced fertility, but may be bred.

The Tg(Pdx1-cre/Esr1*)#Dam transgene contains Cre-ER^TM (Cre recombinase fused to a G525R mutant form of the mouse estrogen receptor ligand binding domain) under the control of the mouse Pdx1 promoter. The Donating Investigator reports that mice homozygous for the Tg(Pdx1-cre/Esr1*)#Dam transgene are viable and fertile.

Development

This triple mutant line was generated by crossing three single mutant strains:
B6.129S4-Kras^tm4Tyj/J Stock No. 008179,
B6.129P2-Trp53^tm1Brn/J Stock No. 008462,
STOCK Tg(Pdx1-cre/Esr1*)#Dam/J Stock No. 024968.

For the Kras^tm4Tyj allele, a targeting vector was designed to place a G12D point mutation in exon 1 of the gene and a loxP-flanked STOP element upstream of the mutation. The STOP element incorporates a PGK-puromycin selection cassette at the 5' end in an opposite directional orientation. An adenoviral strong splice acceptor, typically used in gene trap vectors, is fused upstream of the his3 stuffer fragment to prevent splicing around the stopper (in the case that transcription isn't completely silenced). A mutant splice donor site is on the 3' end and a tetrameric tandem array of SV40 PolyA. The stopper was designed to fit into genomic Sal1 or Xho1 sites. The stop cassette prevents the expression of mutant Kras until it is removed by Cre mediated recombination of the Loxp sites, thus allowing expression of oncogenic Kras. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6 for more than 10 generations by the donating laboratory which verified correct orientation by Southern assays involving 5' and 3' external and internal probes.

For the Trp53^tm1Brn mutation, a targeting vector was used to introduce flanking loxP sites to introns 1 and 10 of the gene. An IB10/E14IB10 129P2/OlaHsd-derived embryonic stem cell line was used to create the mutation. The mice were then backcrossed to C57BL/6 for eight generations.

For the Tg(Pdx1-cre/Esr1*)#Dam transgene, Cre-ER^TM (Cre recombinase fused to a G525R mutant form of the mouse estrogen receptor ligand binding domain) was introduced to the starting ATG of mouse Pdx1, and followed by an SV40 polyadenylation signal. The transgenic vector was injected into B6CBAF1 embryos. Resultant mice were originally crossed with outbred ICR or CD1 animals, then backcrossed to C57BL/6. Subsequent crosses to both ICR/CD1 and C57BL/6 contribute to the STOCK background.

Expression Data

Expressed Gene	cre/Esr1, Cre recombinase and estrogen receptor 1 fusion gene,
Site of Expression	Tamoxifen induction drives mosaic expression of cre recombinase in endocrine, exocrine, and duct tissue of the pancreas.

Control Suggestions

Approximate Controls

None Available (Mice from the colony that are heterozygous for the targeted mutations and noncarrier for the transgene should be considered for use as controls. The most appropriate control animal will depend on the nature of the experiment. )

Additional Information

Considerations for Choosing Controls

Selected References

Maddipati R; Stanger BZ. 2015. Pancreatic Cancer Metastases Harbor Evidence of Polyclonality. Cancer Discov 5(10):1086-97PubMed: 26209539 MGI: J:230607

View All References

Genetics

Trp53^tm1Brn

Allele Symbol: Trp53^tm1Brn

Allele Name	targeted mutation 1, Anton Berns
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	targeted mutation 1, Anton Berns; Trp53^tm1Brn
Gene Symbol and Name	Trp53, transformation related protein 53
Gene Synonym(s)	BCC7; LFS1; p44; P53; TRP53; p53; BMFS5
Strain of Origin	129P2/OlaHsd
Chromosome	11
Molecular Note	Insertion of loxP sites flanking exons 2 through 10. No effect on the normal function of the gene.
Mutations Made By	Dr. Anton Berns, University of Amsterdam

Kras^tm4Tyj

Allele Symbol: Kras^tm4Tyj

Allele Name	targeted mutation 4, Tyler Jacks
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	targeted mutation 4, Tyler Jacks; Kras^tm4Tyj
Gene Symbol and Name	Kras, Kirsten rat sarcoma viral oncogene homolog
Gene Synonym(s)	C-K-RAS; RASK2; CFC2; NS; KRAS1; AI929937; Kras-2; Kras2; Kras-2; KRAS2; Kirsten rat sarcoma oncogene 2, expressed; KI-RAS; NS3; K-ras; K-RAS2B; K-RAS4A; K-RAS4B; K-RAS2A; expressed sequence AI929937; c-Ki-ras; p21; Kras2; Ki-ras; RALD; c-Ki-ras2; K-Ras; OES; K-Ras 2; 'C-K-RAS
Strain of Origin	129S4/SvJae
Chromosome	6
Molecular Note	By homologous recombination in ES cells, the Kras2 locus was targeted with a cassette containing an oncogenic form of the KRAS2 protein in which the glycine at position 12 had been substituted with a an aspartic acid. A loxP flanked stop codon was included upstream of the inserted Kras2 sequence, such that the mutant transcript would be expressed only after cre-mediated recombination.
Mutations Made By	Dr. Tyler Jacks, Massachusetts Institute of Technology

Tg(Pdx1-cre/Esr1*)#Dam

Allele Symbol: Tg(Pdx1-cre/Esr1*)#Dam

Allele Name	transgene insertion, Douglas A Melton
Allele Type	Transgenic (Recombinase-expressing)
Allele Synonym(s)	transgene insertion, Douglas A Melton; Tg(Pdx1-cre/Esr1*)#Dam
Gene Symbol and Name	Tg(Pdx1-cre/Esr1*)#Dam, transgene insertion, Douglas A Melton
Gene Synonym(s)
Promoter	Pdx1, pancreatic and duodenal homeobox 1, mouse, laboratory
Expressed Gene	cre/Esr1, Cre recombinase and estrogen receptor 1 fusion gene,
Site of Expression	Tamoxifen induction drives mosaic expression of cre recombinase in endocrine, exocrine, and duct tissue of the pancreas.
Strain of Origin	(C57BL/6 x CBA)F1
Chromosome	UN
Molecular Note	Sequence encoding a tamoxifen inducible form of a cre recombinase/estrogen receptor fusion protein was adjoined to the Ipf1 promoter to drive mosaic expression of cre recombinase in endocrine, exocrine, and duct tissue of the pancreas. The pound symbol (#) is used when no line is specified and/or lines are pooled.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Cancer Research
  - Cre-lox System
- Cre-lox System
  - Cre Recombinase Expression: Inducible
Cancer Research
- Cre-lox System
  - Cre Recombinase expression: inducible
- Other

Mammalian Phenotype Terms by Genotype

References

Maddipati R; Stanger BZ. 2015. Pancreatic Cancer Metastases Harbor Evidence of Polyclonality. Cancer Discov 5(10):1086-97PubMed: 26209539 MGI: J:230607

Additional - Kras^tm4Tyj related

Additional - Trp53^tm1Brn related

Additional - Tg(Pdx1-cre/Esr1*)#Dam related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Generic Cre Probe
- QPCR:Generic Cre Quantitative PCR
- Probe:Trp53 Probe
- Standard PCR:Generic Cre
- Standard PCR:Trp53
- Standard PCR:Tg(Pdx1-cre/Esr1*)#Dam
- Standard PCR:Generic Cre Melt Curve Analysis
- Standard PCR:Kras Alt1
- Probe:Kras Probe
- QPCR:Tg(Pdx1-cre/Esr1*)#Dam qPCR Alt 1
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

When maintaining a live colony, mice that are heterozygous for the Kras^tm4Tyj allele, homozygous for the Trp53^tm1Brn allele and the Tg(Pdx1-cre/Esr1*)#Dam may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- het, hom, hom
- x WT, hom, hom and recip.
Appearance
- Black or Albino
Citation
When using the KPC, tamoxifen-inducible
mouse strain in a publication, please cite the originating article(s) and include JAX stock #032429 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Please inquire

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.

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Notice to customers in Canada.

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES 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 JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or SERVICES by JACKSON.

Also Known As:KPC, tamoxifen-inducible

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Trp53tm1Brn

Allele Symbol: Trp53tm1Brn

Krastm4Tyj

Allele Symbol: Krastm4Tyj

Tg(Pdx1-cre/Esr1*)#Dam

Allele Symbol: Tg(Pdx1-cre/Esr1*)#Dam

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

References

Additional - Krastm4Tyj related

Additional - Trp53tm1Brn related

Additional - Tg(Pdx1-cre/Esr1*)#Dam related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Trp53^tm1Brn

Allele Symbol: Trp53^tm1Brn

Kras^tm4Tyj

Allele Symbol: Kras^tm4Tyj

Additional - Kras^tm4Tyj related

Additional - Trp53^tm1Brn related