GENETIC IDENTIFICATION OF MOM-1, A MAJOR MODIFIER LOCUS AFFECTING MIN-INDUCED INTESTINAL NEOPLASIA IN THE MOUSE

Mutations in the human APC gene cause various familial colon cancer sy ndromes. The Multiple intestinal neoplasia (Min) mouse provides an exc ellent model for familial colon cancer: it carries a mutant mouse Apc gene and develops many intestinal adenomas. Here, we analyze how this tumor phenotype is dramatically modified by genetic background. We rep ort the genetic mapping of a locus that strongly modifies tumor number in Min/+ animals. This gene, Mom-1 (Modifier of Min-1), maps to dista l chromosome 4 and controls about 50% of genetic variation in tumor nu mber in two intraspecific backcrosses. The mapping is supported by a L OD score exceeding 14. Interestingly, Mom-1 lies in a region of synten y conservation with human chromosome 1p35-36, a region of frequent som atic loss of heterozygosity in a variety of human tumors, including co lon tumors. These results provide evidence of a major modifier affecti ng expression of an inherited cancer syndrome.