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 cloni
ng, now commonly used in the identification of loci affecting a qualit
ative phenotype, has yet to be successfully applied to quantitative tr
ait loci. This study describes the application of candidate gene testi
ng, 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 Apc(Min/+) mice to spontaneous i
ntestinal tumor development. The authors also discuss the further test
ing 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.