Pik3ca (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide; also called PI3K) encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase. It is one of the most frequently mutated genes in human cancer. H1047R mutations in the kinase domain account for approximately 40% of breast cancer PIK3CA mutant alleles.
In this strain, an H1047R mutant form of Pik3ca was targeted to the Gt(ROSA)26Sor locus behind a floxed PGK-Neo stop cassette.
When crossed with an MMTV-Cre strain (see Stocks 003551 and 003553) to excise the floxed stop cassette, mutant Pik3a is expressed in mammary epithelium. Starting at 5 months of age, females develop mammary tumors as well as lymphoid and skin malignancies. The percentage of animals affected by tumors varied based on the particular MMTV-Cre strain used. Mammary tumors were observed in both virgin and multiparous mice. Males were not studied.
When a floxed p53 targeted mutation (e.g. Trp53tm1Brn Stock No. 008462) is introduced to the double mutant (R26-Pik3ca; p53; MMTV-Cre), decreased survival is observed with rapid lymphoma and mammary tumor kinetics.
A small percentage of H1047R mutant mice, in and of themselves (without Cre excision of the floxed stop) show reduced survival due to development of blood vessel lesions. Spontaneous activation or expression in endothelial cells is the suspected cause. The majority of animals have a normal lifespan of 18 months or greater.
