Mice bearing the FLP recombinase-inducible KrasFSFG12V allele may be useful for studying K-RAS driven lung adenocarcinomas.
Dr. Mariano Barbacid, Centro Nacional de Investigaciones Oncol
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), Null/Knockout, Humanized sequence) | Kras | Kirsten rat sarcoma viral oncogene homolog |
KrasFSFG12V mice contain a 5’ frt-flanked STOP-neo cassette, followed by a G12V mutation in the Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene. Ras genes are small GTPases that act downstream of receptors and nonreceptor tyrosine protein kinases in multiple pathways to transfer information to the nucleus. K-ras has been found to be primarily activated in human tumors in pancreatic, colon, and lung cancer. The unrecombined KrasFSFG12V allele is null. Hence, homozygous KrasFSFG12V embryos die at midgestation as the Kras–/– mice. When bred to mice expressing FLP Recombinase, removal of the frt-flanked STOP cassette allows expression of KrasG12V, commonly found in human tumors.
Tracheal infection of these KrasFSFG12V mice with Adeno-FLP particles induces lung adenomas and adenocarcinomas with an incidence and latency similar to that observed in the KrasLSLG12Vgeo mice (Stock No. 026924) infected with Adeno-Cre particles.
Breeding to bitransgenic Elas-tTA/tetO-FLP mice that express FLP recombinase under the control of the elastase promoter in a tet-off system allows selective expression of the KrasG12V oncoprotein in cells of pancreatic acinar lineage. Untreated mice develop PanIN lesions and pancreatic ductal adenocarcinomas with an incidence and latency similar to that observed with KrasLSLG12Vgeo mice carrying the Elas-tTA/tetO-Cre transgenes.
Crossing KrasFSFG12V mice with strains carrying floxed alleles of targets with potential therapeutic value, allows the temporal and spatial separation of tumor development and target ablation. This strategy makes it possible to determine the therapeutic properties of the target in a well established tumors.
A targeting vector was designed to insert a frt-flanked PGK-neo-STOP cassette upstream of the Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) initiation codon. This event also introduced two point mutations in codon 12 of exon 1 (GGT to GTA) replacing a glycine residue with a valine (G12V), a mutation commonly found in human tumors. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females to generate a colony of KrasFSFG12V mice. These mice were bred to C57BL/6.OlaHsd mice for at least 5 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | Kras, Kirsten rat sarcoma viral oncogene homolog, mouse, laboratory |
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Site of Expression | Expression of Krastm3Bbd follows FLP recombination to remove the frt-flanked STOP cassette. |
Allele Name | targeted mutation 3, Mariano Barbacid |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Null/Knockout, Humanized sequence) |
Allele Synonym(s) | KrasFSFG12V |
Gene Symbol and Name | Kras, Kirsten rat sarcoma viral oncogene homolog |
Gene Synonym(s) | |
Expressed Gene | Kras, Kirsten rat sarcoma viral oncogene homolog, mouse, laboratory |
Site of Expression | Expression of Krastm3Bbd follows FLP recombination to remove the frt-flanked STOP cassette. |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 6 |
Molecular Note | A targeting vector was designed to insert a FRT-flanked PGK-neo-STOP cassette upstream of the Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) initiation codon. This event also introduced two point mutations in codon 12 of exon 1 (GGT to GTA) replacing a glycine residue with a valine (G12V), a mutation commonly found in human tumors. |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony. Homozygous embryos die at midgestation.
When using the KrasFSFG12Vgeo mouse strain in a publication, please cite the originating article(s) and include JAX stock #027010 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Kras<tm3Bbd> |
Frozen Mouse Embryo | B6.129-Kras<tm3Bbd>/J | $2595.00 |
Frozen Mouse Embryo | B6.129-Kras<tm3Bbd>/J | $2595.00 |
Frozen Mouse Embryo | B6.129-Kras<tm3Bbd>/J | $3373.50 |
Frozen Mouse Embryo | B6.129-Kras<tm3Bbd>/J | $3373.50 |
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