PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine.

ABSTRACT

BACKGROUND: Therapeutic regulation of PPARdelta activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARdelta) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPARdelta either attenuates or potentiates intestinal neoplasia. To further investigate the PPARdelta dependency of intestinal tumourigenesis, we have analysed the consequences of PPARdelta deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair. METHODS: Mice deficient for both PPARdelta and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded. RESULTS: No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPARdelta does not modify impaired mismatch repair induced neoplasia. CONCLUSION: In contrast with the previously observed acceleration of intestinal neoplasia in the context of the ApcMin/+ mouse, PPARdelta deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPARdelta is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARdelta inactivation may be highly context dependent.