The Mom1(AKR) intestinal tumor resistance region consists of Pla2g2a and alocus distal to D4Mit64

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified d uring a screen for polymorphic modifiers of intestinal tumorigenesis in Apc (Min/+) mice. Here, we demonstrate that the Mom1(AKR) allele consists of tw o genetic components. These include the secretory phospholipase Pla2g2a, wh ose candidacy as a Mom1 resistance modifier has now been tested with severa l transgenic Lines. A second region, distal to Pla2g2a, has also been ident ified using fine structure recombinants. Pla2g2a(AKR) transgenic mice demon strate a modest resistance to tumorigenesis in the small intestine and a ve r! robust resistance in the large intestine, Moreover, the tumor resistance in the colon of Pla2g2a(AKR) animals is dosage-dependent, a finding that i s 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 phenoty pes of these two modifier loci are complementary, both in their quantitativ e and regional effects. The additive effects and tight Linkage of these mod ifiers may have been necessary for the initial identification of the Mom1 r egion.