These models enable researchers to study the onset, progression of the disease, and understand in depth the molecular events that contribute to the development and spread of colorectal cancer.
They also provide a valuable biological system, to simulate human physiological conditions, suitable for testing therapeutics.
[1][2][3] Familial Adenomatous Polyposis (FAP) is a hereditary disease that is characterized with development of numerous colon polyps.
[8] More recently a new mutant Apc mouse model was constructed in which multiple polyps form in the distal colon.
[11] Today we know that the beta-catenin protein (part of the Wnt signaling pathway) is implicated in colorectal carcinogenesis and its stability in the cell is regulated by APC.
[12] The conditional stabilizing mutation in the beta-catenin gene caused formation of up to 3000 polyps in the small intestine of this mouse model.
A mouse model carrying mutations in ApcΔ716 and Smad4 (mothers against decapentaplegic homolog 4) is characterized with development of invasive adenocarcinomas.
[20] Yet these adenocarcinomas do not metastasize and their histopathology is similar to that of the right side colon cancer in human with frequent mutation of the type II receptor for TGF-β.
Mice with mutations in transforming growth factor-β1 gene introduced into 129/Sv Rag2 mutant mouse [21] accelerates adenocarcinomas with strong local invasion suggesting a role for genetic background in tumor development.
[23] Treatment of this mouse model with the procarcinogen azoxymethane (AOM) leads to formation of dysplastic microadenomas in the proximal but not in the distal colon.
[25] Mutant mice for interleukin 2 and beta microglobulin genes also produce ulcerative colitis-like phenotype and develop adenocarcinomas in the colon.
However, in mice fed diet plus DOC plus the antioxidant chlorogenic acid, the frequency of colon cancer was reduced.