These p85β mutant mice harbor a "knockout" allele of the phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) locus. These mutant mice may be useful in generating conditional mutations for studying class IA phosphoinositide 3-kinases (PI3Ks) in cell growth, cell proliferation cell survival signaling, insulin signaling and tumor angiogenesis, as well as genomic aberrations that promote tumorigenesis/cancer through upregulation of the PI3K/AKT signaling axis.
Lewis C Cantley, Beth Israel Deaconess Medical Center
Mice homozygous for the p85β "knockout" allele are viable and fertile, with no protein expression in liver or muscle from the targeted gene. Phosphoinositide 3-kinases (PI3K) activity associated with p85β is abolished in liver and muscle from homozygous mice. p85β-null mice exhibit significantly lower glucose levels (both fasting and fed states), decreased plasma insulin concentrations (fed state), and significantly improved glucose-lowering effect after intraperitoneal insulin injection compared to wildtype mice. PKB/AKT activity is significantly upregulated in muscle (but not liver) from p85β-deficient mice. These mutant mice may be useful for studying class IA phosphoinositide 3-kinases (PI3Ks) in cell growth, cell proliferation cell survival signaling, insulin signaling and tumor angiogenesis, as well as genomic aberrations that promote tumorigenesis/cancer through upregulation of the PI3K/AKT signaling axis.
When these p85β mutant mice are bred with p85α mutant mice (Stock No. 012871) and Tie2-Cre transgenic mice (Stock No. 004128), the resulting multiple mutant mice may be used to study vascular integrity during development and tumor neovascularization/angiogenesis.
When these p85β mutant mice are bred with p85α mutant mice (Stock No. 012871) and MCK-Cre transgenic mice (Stock Nos. 006405 or 006475), the resulting multiple mutant mice may be used to study protection from cardiac hypertrophy.
A targeting vector was designed to replace a 1.8 kb region of the Pik3r2 locus (including 5'-untranslated sequence, the start codon, and the first exon) with a pgk-neomycin resistance cassette. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6NCrl females to establish the colony. Mice heterozygous for the p85β- mice on a mixed genetic background (C57BL/6, 129Sv, FVB/N, and maybe others) were sent to The Jackson Laboratory Repository (see additional information below). Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the p85β- colony.
Prior to arrival at The Jackson Laboratory Repository, p85β- mice were also bred with Cre recombinase-expressing mice, conditional EGFP-expressing mice, and Pik3r1 mutant mice (Stock No. 012871); this results in the mixed genetic background (C57BL/6, 129Sv, FVB/N, and maybe others). The donating investigator reports that the mice did not harbor Cre recombinase when they were sent to The Jackson Laboratory Repository. Colony managers here at The Jackson Laboratory Repository will assay the mice (and selectively breed away any unwanted mutant alleles, if necessary) to maintain the p85β- colony.
|Allele Name||targeted mutation 1, Lewis C Cantley|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||p85beta-; Pik3r2-|
|Gene Symbol and Name||Pik3r2, phosphoinositide-3-kinase regulatory subunit 2|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A targeting construct was designed to replace the 5' UTR, start codon and first exon with a PGK-neo cassette.|
|Mutations Made By|| |
Lewis Cantley, Beth Israel Deaconess Medical Center
When maintaining a live colony, homozygous mice may be bred together.
When using the STOCK Pik3r2tm1Lca/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012872 in your Materials and Methods section.