Tumor burden and clonality in multiple intestinal neoplasia mouse/normal mouse aggregation chimeras

Aggregation chimeras were formed between C57BL/6 mice heterozygous for the Apc(min) (Min) mutation and wild-type SWR mice, that differ in their Pla2g2 a status, a modifier of Apc(min), and also in their resistance to intestina l polyp formation. Variation in the dolichos biflorus agglutinin-staining p atterns of the intestines of these mouse strains was used to determine the chimeric composition of the intestine in individual mice and to examine the clonal composition of adenomas. Macroscopic adenoma numbers in chimeric mi ce were compared with the expected adenoma numbers based on the percentage of C57BL/6J-Apc(min/+) epithelium in individual mice. These results unexpec tedly show that there was no apparent inhibitory effect of the sWR-derived (Pla2g2a wildtype) tissue on adenoma formation in the C57BL/6J-Apc(min/+) e pithelium. This suggests that the main genetic modifiers of the Min phenoty pe act at a cellular or crypt-restricted level with no discernable systemic effect. All adenomas were seen to contain C57BL/6J-Apc(min/+)-derived epit helium. confirming that the germline mutation of the mApc gene is necessary to initiate tumorigenesis in this model system, and that the mApc gene act s in a cell autonomous fashion.