Pik3ca RBD mutant Mouse

Tool Details

*FOR RESEARCH USE ONLY

• Tool name: Pik3ca RBD mutant Mouse
• Tool sub type: Mouse
• Disease: Cancer
• Model: Mutant
• Conditional: No
• Description: In vivo study of p110alpha disruption and Ras signalling;
• Genetic background: A Pi3kca targeting vector, containing substitutions at residues 208 (T to D) and 227 (K to A) and a loxP flanked resistance cassette, was transfected into 129 ES cells. Properly targeted ES cells containing a homologous recombination event were selected, cloned and injected into C57BL6 blastocysts. Chimeric offspring were backcrossed to establish heterozygous mice, which were subsequently mated to Cre transgenic mice to excise the resistance cassette. Heterozygous Pik3ca mice were interbred to establish homozygous mutants.
• Phenotype: Pi3kca mice express a mutated knockin form of PI-3kinase alpha (one of the main effectors of Ras signalling) which is no longer able to associate with Ras. This knockin mutation greatly increases the tumour resistance of Pi3kca mice to chemically- and K-Ras-induced tumourigenesis. In addition, the mice could be used to study the role of Ras-PI-3K signalling in inflammation, cytoskeletal reorganisation and cell motility.Pi3kca mice demonstrate deficient development and branching of the lymphatic system compared to wildtype mice
• Strain: B6.129S7(Cg)-Pik3catm1Jdo/J
• Production details: A Pi3kca targeting vector, containing substitutions at residues 208 (T to D) and 227 (K to A) and a loxP flanked resistance cassette, was transfected into 129 ES cells. Properly targeted ES cells containing a homologous recombination event were selected, cloned and injected into C57BL6 blastocysts. Chimeric offspring were backcrossed to establish heterozygous mice, which were subsequently mated to Cre transgenic mice to excise the resistance cassette. Heterozygous Pik3ca mice were interbred to establish homozygous mutants.
• Additional notes: The Pi3kca mouse is an ideal tool for studying cell signalling and the development of Ras or PI-3K inhibitors. Pi3kca mice express a mutated knockin form of PI-3kinase alpha (one of the main effectors of Ras signalling) which is no longer able to associate with Ras. This knockin mutation greatly increases the tumour resistance of Pi3kca mice to chemically- and K-Ras-induced tumourigenesis. In addition, the mice could be used to study the role of Ras-PI-3K signalling in inflammation, cytoskeletal reorganisation and cell motility. Pi3kca mice demonstrate deficient development and branching of the lymphatic system compared to wildtype mice. Full mouse strain name B6.129S7(Cg)-Pik3catm1Jdo/J

Handling

• Shipping conditions: Embryo/Spermatoza- Dry Ice

Target Details

• Target: Phosphoinositide 3-Kinase C alpha (PI 3kinase) / p110alpha mutant (disrupted Ras interaction)

References

• Gupta et al. 2007. Cell. 129(5):957-68. PMID: 17540175.
• Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice.