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

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582 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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Dietrich, W. F., Lander, E. S., Smith, J. S., Moser, A. R., Gould, K. A., Luongo, C., Borenstein, N., & Dove, W. (1993). Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell, 75(4), 631-639. https://doi.org/10.1016/0092-8674(93)90484-8