Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse

William F. Dietrich, Eric S. Lander, Jennifer S. Smith, Amy R. Moser, Karen A. Gould, Cindy Luongo, Natalie Borenstein, William Dove

Research output: Contribution to journalArticlepeer-review

627 Scopus citations

Abstract

Mutations in the human APC gene cause 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.

Original languageEnglish (US)
Pages (from-to)631-639
Number of pages9
JournalCell
Volume75
Issue number4
DOIs
StatePublished - Nov 19 1993
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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