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The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. Oncogene 2000 Jun 29;19(28):3182-92

Date

08/02/2000

Pubmed ID

10918573

DOI

10.1038/sj.onc.1203646

Scopus ID

2-s2.0-0034729532 (requires institutional sign-in at Scopus site)   95 Citations

Abstract

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during a screen for polymorphic modifiers of intestinal tumorigenesis in ApcMin/+ mice. Here, we demonstrate that the Mom1AKR allele consists of two genetic components. These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines. A second region, distal to Pla2g2a, has also been identified using fine structure recombinants. Pla2g2aAKR transgenic mice demonstrate a modest resistance to tumorigenesis in the small intestine and a very robust resistance in the large intestine. Moreover, the tumor resistance in the colon of Pla2g2aAKR animals is dosage-dependent, a finding that is consistent with our observation that Pla2g2a is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier demonstrate a modest tumor resistance that is confined to the small intestine. Thus, the phenotypes of these two modifier loci are complementary, both in their quantitative and regional effects. The additive effects and tight linkage of these modifiers may have been necessary for the initial identification of the Mom1 region.

Author List

Cormier RT, Bilger A, Lillich AJ, Halberg RB, Hong KH, Gould KA, Borenstein N, Lander ES, Dove WF

Author

Amy Jeanette Prunuske PhD Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenomatous Polyposis Coli
Adenomatous Polyposis Coli Protein
Animals
Cytoskeletal Proteins
Female
Goblet Cells
Humans
Immunity, Innate
Intestines
Male
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Transgenic
Phospholipases A