Jeena Choi with Dr. Amy Moser, Hua Wang, and Doug Teske

UW-Madison Medical School, Department of Human Oncology

An autosomal dominantly inherited mutation in the adenomatous polyposis coli (Apc) gene on chromosome 5q21 leads to familial adenomatous polyposis (FAP) syndrome in humans.  FAP patients are predisposed to develop hundreds of adenomatous polyps in their colon, which typically lead to inevitable colon cancer in the patient if not removed.  Multiple intestinal neoplasia (Min) mice are an excellent model for the study of FAP because they are heterozygous for ApcMin/+, a germ-line mutation characterized by the growth of several colorectal polyps, and are available in inbred strains.  Studying the development of intestinal and colorectal tumors in laboratory mice will give us an understanding of the genetic components that affect the development of FAP in humans.  Mice were treated with ethylnitrosourea at 35 days of age, euthanized at 100 days, and genotyped using PCR. Observation of intestinal tumors displayed a significantly large multiplicity in the proximal colon of FVB Congenic ApcMin/+ mice, leading us to study FVBxB6 F1 ApcMin/+ backcross mice to determine if any modifier genes could be mapped.  Statistical analysis of tumor multiplicity for homozygosity and heterozygosity for resistant and sensitive alleles at several markers in chromosomes 4, 6, and 9 confirmed the presence of a previously mapped gene, Mom1, and suggested the presence of a new recessive modifier gene.  The gene demonstrates an additive effect on tumor number, corresponding to the addition of resistant or sensitive alleles, and on tumor location, positioning them largely in the proximal colon.