These p110αflox (p110alphaflox) 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.
