• 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.
• 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.
• When crossed with mice expressing Cre recombinase driven by tissue-specific promoters, Cre-mediated recombination excises the LSL element, enabling production of the mutant KRAS oncogenic protein. This model system serves as a valuable tool for investigating cancer pathogenesis and developmental processes.

Gene targeting strategy for B-Kras-LSL-G12D mice. A targeting vector was designed to place a G12D point mutation in exon 2 of the mouse 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.