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

Cell. 1993 Nov 19;75(4):631-9. doi: 10.1016/0092-8674(93)90484-8.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Animals
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1
  • Colonic Neoplasms / genetics*
  • Genes, Dominant
  • Genes, Tumor Suppressor*
  • Humans
  • Mice / genetics*
  • Mice, Mutant Strains
  • Neoplasms, Experimental / genetics