Familial adenomatous polyposis (FAP) is a rare autosomal dominant genetic disease, which is characterized by multiple colorectal adenomatous polyps. It is be caused by a functional mutation in the adenomatous polyposis coli (APC) gene. In order to investigate the syndrome in vivo, APCMin+/- mice were developed, imitating the polyp phenomenon in humans. In previous studies, Min+/- mouse was used for identifying modifiers for APC gene. To date a number of the modifiers of APC genes have been mapped (MOM 1-10), but their genes are not identified, yet. Based on our recent research, we have confirmed that Collaborative Cross (CC) mice to be powerful tool for finding the genes responsible for the different phenotypic variances including the FAP. In this research C57Bl/6J male mice, carry APCMin-/+ were mated with female mice from 31 CC lines. The litters carrying APC mutant gene were sacrificed after 5 months maintenance on standard mouse diet at conventional facility, and the small intestines and colon were extracted for polyp counts. The size, number and locations of polyps were recorded. The results of the scan were used as a quantitative trait for mapping of modifier for APC gene. Our results have shown significant variations in the numbers and locations of the polyps in the small intestine and colon between different CC lines. Broad sense heritability was calculated and found to be 0.45. Initial QTL mapping was conducted and a strong Locus was mapped on the proximal region of chromosome 15 (Mmu15). A number of candidate genes were identified and will be presented at the meeting.
