The aim was to establish a genetic, colon-specific, and more human-like CRC model driven by loss of K8 and adenomatous polyposis coli (Apc).<h4>Methods</h4>Colon-specific targeting using CDX2P-CreER<sup>T2</sup> mice was used to generate K8<sup>flox/flox</sup>; CDX2P-CreER<sup>T2</sup> and K8<sup>flox/flox</sup>; CDX2P-CreER<sup>T2</sup>; Apc<sup>flox/+</sup> mice. Here, KRT8 is linked to colorectal carcinoma.