The Kirsten rat sarcoma viral oncogene homolog (KRAS) is a proto-oncogene encoding the K-Ras protein, a membrane-associated GTPase, and a key member of the RAS gene family. K-Ras protein plays a crucial role in the RAS/MAPK signaling pathway by regulating the interconversion between GTP and GDP, transmitting extracellular signals to the nucleus, and thus influencing cell growth, proliferation, and differentiation ^[1]. KRAS is among the most frequently mutated genes in cancer, with mutations at codons 12, 13, and 61 leading to constitutive activation of the K-Ras protein. These alterations interact with multiple effector molecules and activate downstream signaling pathways, resulting in uncontrolled cellular proliferation and oncogenesis ^[2]. Approximately 30% of cancer patients harbor KRAS mutations. Specifically, 90% of pancreatic cancers, 50% of colorectal cancers, 25% of lung cancers, and 20–30% of non-small cell lung cancers (NSCLC) exhibit KRAS mutations. The G12C mutation is one of the most common KRAS mutations, accounting for 33% of all KRAS mutations, and is particularly prevalent in NSCLC. The G12C mutation is also present in approximately 14% of pancreatic cancers, 3–4% of colorectal cancers, and 1–2% of cholangiocarcinomas ^[3].

This strain is a conditional expression model of K-ras G12C, generated by introducing the G12C point mutation into the mouse Kras gene. Under normal conditions, the expression of K-ras G12C is blocked by an upstream loxP-Stop-loxP cassette. Expression is achieved only upon crossing with Cre mice, where Cre recombinase-mediated loxP site recombination removes the blocking sequence. This enables precise temporal and spatial control of K-ras G12C expression and tumorigenesis. By mating with tissue-specific Cre mice, this model can conditionally express K-ras G12C in specific tissues, making it a valuable tool for constructing cancer models in various tissues and organs. Homozygous LSL-K-ras G12C mice are nonviable.