Disease model: familial adenomatous polyposis

Mutations in the APC gene are responsible for familial adenomatous polyposi s (FAP) and for the majority of sporadic colorectal cancers. The establishm ent of genotype-phenotype correlations in FAP is often complicated by the g reat clinical variability observed among carriers of the same APC mutation even within the same kindred. This variability is likely to arise from the interaction of genetic and environmental modifying factors, the dissection of which ideally requires the employment of mouse models where the effects of specific Apc mutations are analyzed in an inbred, homogeneous genetic ba ckground and a controlled environment. The availability of different Apc mo use models allows not only the establishment of more precise genotype-pheno type correlations but has also provided very important clues for the unders tanding of the function of APC in homeostasis and tumorigenesis. Also, the close phenotypic resemblance to the human disease makes these mice unique p reclinical models to test chemopreventive and therapeutic interventions.