Mouse models for colorectal cancer

Abstract

A large number of mouse models have been developed for colorectal cancer (CRC). In this chapter, we describe the initial knockout models made by insertional mutagenesis for the Adenomatous polyposis coli gene (Apc) and Mismatch Repair genes, and the subsequent creation of conditional knockout models for tissue- and site-specific removal of Apc (Apc CKO), Msh2(Msh2 CKO), and Mlh1(Mlh1 CKO). We also describe the development of a model for sporadic tumors of the distal colon through the surgical infusion of Adenoviral-Cre into Apc CKO mice, and the ability to follow these tumors that mimic the human condition quite well, by colonoscopy. The features of these models are presented as are the expectations of their use in chemotherapy, the identification of pertinent CRC pathways, and possible points of intervention. Methods of imaging are described that permit the observation of progressive tumor growth or response to chemotherapeutic agents.