Action of Min and Mom1 on neoplasia in ectopic intestinal grafts.

Mice heterozygous for Mm, a mutant allele of Apc, develop adenomas throughout the intestinal tract. Tumor multiplicity in Mm mice is influenced by genetic modifier loci. Previously, we mapped one of these modifier loci, Moml, to distal mouse chromosome 4. Moml is a semidominant modifier of both tumor size and multiplicity in Mm mice. Recent evidence suggests that Momi may encode a secretory phospholipase, PIa2g2a. Pla2g2a is expressed in a variety of cell types and seems to be involved in inflammatory responses and bacterial defense mechanisms. Here, we determine whether Mm and Momi act in a tissueautonomous fashion using ectopic intestinal isografts. Within the small intestinal grafts, both Mm and Momi act in a tissue-autonomous manner. There is no evidence that either Mm or Moml has a systemic effect on tumor development. However, within the colonic grafts, the Mm phenotype does not appear to be autonomous; the development of colonic tumors in Mm mice seems dependent on factors beyond the Mm genotype of the colonic epithelium. Microenvironmental factors, such as digestive secretions, dietary components, or intestinal flora, may be critical factors contributing to the development of Mm-induced