Analysis of the Mom1 modifier of intestinal neoplasia in mice

Although the methodology for mapping genes controlling susceptibility to tumor development in mice is becoming well established, it remains a formidable challenge to move from linkage to locus. Positional cloning, now commonly used in the identification of loci affecting a qualitative phenotype, has yet to be successfully applied to quantitative trait loci. This study describes the application of candidate gene testing, a method complementary to positional cloning. The method has been applied to evaluate candidates for the quantitative trait locus, Mom1, which modifies the susceptibility of ApcMin/+ mice to spontaneous intestinal tumor development. The authors also discuss the further testing of one candidate, the phospholipase gene Pla2g2a, by transgenesis. Finally, studies on the mode of action of Mom1 are discussed in light of the evidence that Mom1 encodes this secretory phospholipase.