EXPERIMENTAL MODELS
Contributor Information
- Name Julian Downward
- Institute Cancer Research UK, London Research Institute: Lincoln's Inn Fields
Tool Details
- Tool name: Pik3ca RBD mutant Mouse
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Cancer
- Model: Mutant
- Conditional: No
- Cell signalling pathway: PI3K/AKT signalling
- Genetic background and cross history: 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
- Description: In vivo study of p110alpha disruption and Ras signalling;
- Research area: Cancer; Cell signaling and signal transduction; Genetics
- 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
- For Research Use Only
Target Details
- Target: Phosphoinositide 3-Kinase C alpha (PI 3kinase) / p110alpha mutant (disrupted Ras interaction)
Application Details
Handling
- Shipping conditions: Embryo/Spermatoza- Dry Ice
Documentation
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.
.svg)
Availability: 
.svg)
.svg)
