Cell
Volume 75, Issue 4, 19 November 1993, Pages 631-639
Journal home page for Cell

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

https://doi.org/10.1016/0092-8674(93)90484-8Get rights and content

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.

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