This KrasLSL-G12D strain carries a Lox-Stop-Lox (LSL) sequence followed by the K-ras G12D point mutation allele commonly associated with human cancer. When bred to a strain expressing Cre recombinase under control of various tissue specific promoters, Cre recombination deletes the LSL cassette and allows the expression of the mutant KRAS oncogenic protein. This strain may be useful in studies of cancer and development.
Dr. Tyler Jacks, Massachusetts Institute of Technology
This KrasLSL-G12D strain carries a point mutation (G12D) whose expression is blocked by the presence of a loxP-flanked stop codon. Homozygotes die in utero. Cre-mediated recombination can excise the stop codon and permit the oncogenic protein to be expressed. Intranasal infection with an adenovirus encoding Cre results in a very high frequency of lung tumors and permits controlled timing of tumor initiation and tumor multiplicity. This strain may be useful in studies of cancer and development.
When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element and a strain expressing a tetracycline-controlled activator protein in lung epithelial cells (see Stock No. 006234 and 006235 respectively), this mutant mouse strain may be useful in studies of lung development.
When bred to a strain expressing interferon inducible Cre recombinase (see Stock No. 003556, 005673 for example), this mutant mouse strain may be useful in studies of Ras and myeloproliferative disease.
When bred to a strain expressing Cre recombinase in mammary gland, skin, and other secretory glands (see Stock No. 003553 for example), this mutant mouse strain may be useful in studies of epithelial hyperplasias.
When bred to a strain expressing Cre recombinase in epiblast derived tissues (see Stock No. 003755 for example), this mutant mouse strain may be useful in studies of Ras and embryonic development.
When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of intrahepatic cholangiocarcinoma.
When bred to a strain expressing Cre recombinase in myeloid cell lineage (see Stock No. 004781 for example), this mutant mouse strain may be useful in studies of lung cancer.
When bred to a strain expressing tamoxifen-inducible Cre recombinase in melanocytes (see Stock No. 012328 for example), this mutant mouse strain may be useful in studies of melanomagenesis.
When bred to a strain expressing Cre recombinase in astrocytes (see Stock No. 012887 for example), this mutant mouse strain may be useful in studies of neurofibroma development.
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.
|Allele Name||targeted mutation 4, Tyler Jacks|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||K-Ras(G12D)fl; K-RasL; K-RasG12D; K-rasLSL; KR; Kras2tm4Tyj; Kras2tm14Tyj; KrasG12D; KrasLSL-G12D; KrasLox; LSL-K-ras G12D; LSL-K-rasG12D; LSL-Kras G12D; LSL-KrasG12D; LSL-KrasG12D; Lox-Stop-Lox-KrasG12D; caKRas|
|Gene Symbol and Name||Kras, Kirsten rat sarcoma viral oncogene homolog|
|Gene Synonym(s)||AI929937; C-K-RAS; CFC2; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; K-Ras; K-ras; KI-RAS; KRAS1; KRAS2; Ki-ras; Kirsten rat sarcoma oncogene 2, expressed; Kras-2; Kras-2; Kras2; Kras2; NS; NS3; RALD; RASK2; c-Ki-ras; c-Ki-ras2; expressed sequence AI929937; p21|
|Strain of Origin||129S4/SvJae|
|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
When maintained as a live colony, heterozygotes may be bred. Homozygotes are embryonic lethal.
When using the LSL-K-ras G12D mouse strain in a publication, please cite the originating article(s) and include JAX stock #008179 in your Materials and Methods section.
|Heterozygous or Wild-Type for Kras<tm4Tyj>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.
"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.
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.
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.
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.
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.