FVB.129S6-Gt(ROSA)26Sor^{tm1(Pik3ca*H1047R)Egan}/J

Stock number: 016977
Product name: R26-Pik3ca^H1047R
Research areas: Cancer Research, Research Tools

Description

This R26-Pik3ca^H1047R strain carries a floxed transcriptional stop cassette upstream of the H1047R mutant allele of Pik3ca within the Gt(ROSA)26Sor locus. When crossed with an MMTV-Cre strain, progeny develop mammary tumors as well as lymphoid and skin malignancies.

Detailed description

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. Trp53^tm1Brn 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.

Development

An H1047R Pik3ca mutant allele was targeted to intron 1 of the Gt(ROSA)26Sor gene behind a floxed PGK-Neo stop cassette. This mutation was created in 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Resultant mice were backcrossed to FVB for 12 generations by the donating laboratory.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(Pik3ca*H1047R)Egan}
Name: targeted mutation 1, Sean E Egan
MGI accession ID: MGI:5000472
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence
Synonyms: R26-Pik3ca^H1047R
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Marker synonyms: beta geo; Gtrgeo26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1
Chromosome: 6
Strain of origin: 129S6/SvEvTac
Expressed genes: Pik3ca,phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha,mouse, laboratory
Molecular note: The following sequences were inserted into intron 1: splice acceptor site, a STOP cassette (loxP site flanked neomycin resistance gene cassette), Pik3ca cDNA sequence where histidine codon 1047 (CAT) was changed to arginine (p.H1047R), and bovine GH poly(A) signal sequences.