B6N.129-Pik3ca^tm1Jjz/J

Stock number: 017704
Research areas: Cancer Research, Cardiovascular Research, Diabetes and Obesity Research, Metabolism Research, Research Tools

Description

These p110α^flox (p110alpha^flox) mice possess loxP sites flanking exon 1 of the phosphatidylinositol 3-kinase, catalytic, alpha polypeptide (Pik3ca) gene. This strain may be useful for studying insulin signaling, hepatic glucose and lipid metabolism, and oncogenic transformation.

Detailed description

These p110α^flox (p110alpha^flox) mice possess loxP sites flanking exon 1 of the phosphatidylinositol 3-kinase, catalytic, alpha polypeptide (Pik3ca) gene. P110α is an isoform of the p110 catalytic subunit of PI3K, which is a critical enzyme in the insulin signaling pathway. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 1 deleted in cre-expressing tissues. For example, when crossed to a strain expressing Cre recombinase in the liver, this mutant mouse strain displays reduced insulin sensitivity, impaired glucose tolerance, and increased gluconeogenesis, hypolipidemia, and hyperleptinemia. They also exhibit a 34% reduction in serum free fatty acids, a 28% reduction in total serum cholesterol, and a 44% reduction in serum triglycerides, as well as decreased lipogenic gene expression and hepatic triglyceride content. Their level of serum leptin and leptin receptor expression are increased 8 fold compared to control mice. This strain may be useful for studying insulin signaling, hepatic glucose and lipid metabolism, and oncogenic transformation.

Development

A targeting vector was designed to insert a loxP site upstream of exon 1, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site were placed downstream of exon 1 of the phosphatidylinositol 3-kinase, catalytic, alpha polypeptide (Pik3ca) gene. The construct was electroporated into 129 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a pCAGGS-FLPe expression plasmid to delete the neo cassette. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred to C57BL/6NTac females. These p110α^flox mice were backcrossed to C57BL/6NTac for at least 10 generations. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

Allele

Symbol: Pik3ca^tm1Jjz
Name: targeted mutation 1, Jean J Zhao
MGI accession ID: MGI:3691486
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Pik3ca
Marker name: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
Chromosome: 3
Strain of origin: 129
Molecular note: Exon 1 was flanked by lox P sites, with an FRT-flanked selection cassette between exon 1 and the downstream loxP site. The selection cassette was subsequently removed from the locus via transient transfection with a FLP recombinase plasmid.