KPC

The KPC mouse is an established and clinically relevant model of pancreatic ductal adenocarcinoma (PDAC) which develops many key features observed in human PDAC including pancreatic intraepithelial neoplasia alongside a robust inflammatory reaction including exclusion of effector T cells. Metastases are observed in around 80% of KPC animals located primarily in the liver and lungs. Mutations in both KRAS and TP53 genes are found in around 80% and 70% of all human PDACs respectively. Trp53-R172H、Kras-LSL-G12D were crossed with Pdx1-Cre-Tg to generate KPC mice. The KPC mouse contains a dominant negative point mutation in the transformation related protein 53 gene (TP53R172H), and a conditional activation point mutation in the KRAS gene (KRASG12D). A lox-stop-lox termination sequence is encoded upstream of KRAS mutated genes to prevent expression in the absence of Cre recombinase. The pancreas-specific Pdx-1 promoter enables expression of Cre recombinase in acini, islet and duct cells of the pancreas. Cre-mediated recombination excises the lox-stop-lox termination sequences and enables expression of KRASG12D in pancreatic tissue.