• KRAS, also called p21, is a member of the Ras superfamily of proteins. It is located on human chromosome 12, contains four coding exons and a 5' non-coding exon. KRAS is a membrane-anchored guanosine triphosphate/guanosine diphosphate (GTP/GDP)-binding protein and is widely expressed in most human cells. Like other members of the Ras family, the KRAS protein is a GTPase, and it is involved in intracellular signal transduction and mainly responsible for EGFR-signaling activation. KRAS mutations have been found in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma.
• Trp53 acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process.
• B-KP flox mice can be crossed with Cre under different tissue-specific promoters to achieve expression in specific tissues, can be value the preclinical efficacy of chemotherapies

Gene targeting strategy for B-KP flox mice.

A targeting vector was designed to place a G12D point mutation in exon 2 of the Kras gene, the loxP-flanked STOP element is located upstream of point mutations. The stop cassette prevents the expression of mutant Kras until it is removed by Cre mediated recombination of the Loxp sites, thus allowing expression of oncogenic Kras.

A targeting vector was designed to place a R172H point mutation in exon 5 of the Trp53 gene, the loxP-flanked STOP element is located upstream of point mutations. The stop cassette prevents the expression of mutant Trp53 until it is removed by Cre mediated recombination of the loxP sites, thus allowing expression of oncogenic Trp53.

B-KPC mice are derived from crossing B-KP flox mice with Pdx-1-cre mice

H&E staining of pancreas tissues in B-KPC mice.

The Pdx-driven expression cassette enables tissue-specific expression of Cre recombinase in the pancreas, excising the "Stop" sequence flanked by a pair of loxP sites, there by initiating the expression of the Kras*G12D and Trp53*R172H genes.

Pancreas tissues of C57BL/6 mice (+/+) (Female, 10w, 16w, 18w, n=3) and B-KPC mice (H/+) (Female, 10w, 16w, 18w, n=3)  were collected and analyzed with H&E staining. The results show that B-KPC mice are consistent with pancreatic ductal adenocarcinoma (PDAC).