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

WF Dietrich, ES Lander, JS Smith, AR Moser, KA Gould… - Cell, 1993 - cell.com
WF Dietrich, ES Lander, JS Smith, AR Moser, KA Gould, C Luongo, N Borenstein, W Dove
Cell, 1993cell.com
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 Apt 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 Mid+ animals.
This gene, Morn-l (Modifier of Min-1), maps to distal chromosome 4 and controls about 50 …
Summary
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 Apt 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 Mid+ animals. This gene, Morn-l (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-l lies in a region of synteny conservation with human chromosome 1~ 35-36, 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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