title: Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse.
abstract: Mutations in the human APC gene caused various familial colon cancer syndromes. The Multiple intestinal neoplasia (Min) mouse provides an excellent 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 report the genetic mapping of a locus that strongly modifies tumor number in Min/+ animals. This gene, Mom-1 (Modifier of Min-1), maps to distal chromosome 4 and controls about 50% of genetic variation in tumor number in two intraspecific backcrosses. The mapping is supported by a LOD score exceeding 14. Interestingly, Mom-1 lies in a region of synteny conservation with human chromosome 1p35-36, a region of frequent somatic loss of heterozygosity in a variety of human tumors, including colon tumors. These results provide evidence of a major modifier affecting expression of an inherited cancer syndrome.
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
authors.forename: W F
authors.initials: WF
authors.lastname: Dietrich
authors.forename: E S
authors.initials: ES
authors.lastname: Lander
authors.forename: J S
authors.initials: JS
authors.lastname: Smith
authors.forename: A R
authors.initials: AR
authors.lastname: Moser
authors.forename: K A
authors.initials: KA
authors.lastname: Gould
authors.forename: C
authors.initials: C
authors.lastname: Luongo
authors.forename: N
authors.initials: N
authors.lastname: Borenstein
authors.forename: W
authors.initials: W
authors.lastname: Dove
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000818:Animals; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003110:Colonic Neoplasms / Q000235:genetics*; D005799:Genes, Dominant; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice / Q000235:genetics*; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000235:genetics