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 journalArticle

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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

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Tumors
Neoplasms
Chromosomes
Genes
Colonic Neoplasms
Conservation
Animals
Modifier Genes
APC Genes
Synteny
Chromosomes, Human, Pair 4
Loss of Heterozygosity
Human Chromosomes
Adenoma
Colon
Phenotype
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. / Dietrich, William F.; Lander, Eric S.; Smith, Jennifer S.; Moser, Amy R.; Gould, Karen A; Luongo, Cindy; Borenstein, Natalie; Dove, William.

In: Cell, Vol. 75, No. 4, 19.11.1993, p. 631-639.

Research output: Contribution to journalArticle

Dietrich, WF, Lander, ES, Smith, JS, Moser, AR, Gould, KA, 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, vol. 75, no. 4, pp. 631-639. https://doi.org/10.1016/0092-8674(93)90484-8
Dietrich, William F. ; Lander, Eric S. ; Smith, Jennifer S. ; Moser, Amy R. ; Gould, Karen A ; Luongo, Cindy ; Borenstein, Natalie ; Dove, William. / Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. In: Cell. 1993 ; Vol. 75, No. 4. pp. 631-639.
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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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