Differential susceptibility to colonic ulceration in mice with genetic deletion of Ptges

Prostaglandin E2(PGE2) exerts pleiotropic effects on inflammation, cancer, and maintenance of mucosal homeostasis. A global knockout (KO) of the PGE2 synthase, Ptges, results in the spontaneous development of colonic ulcer in strain A mice (A/D:KO), a phenotype that is largely absent in C57BL/6 mice (B6D:KO) with the same genetic deletion. Gene expression profiling of normal colonic mucosa several weeks prior to the onset of active disease identified a number of signaling pathways that may contribute to mucosal injury in the strain A mice, including the activation of inflammatory networks and antibacterial responses. Alterations toseveral microbial species includeAkkermansia muciniphilaandBacteroides vulgatus, likely associated with dysregulation of short chain fatty acid (SCFA) synthesis. These results suggest that absence ofPtgescauses a dramatic shift in the inflammatory milieu in strain A mice, an effect thatmay result from unremitting bacterial infections, triggered in part by dysregulation of epithelial homeostasis and a subtle defect in intrinsic immune regulation. To identify differentially expressed genes that may be associated with the divergent susceptibility to colonic ulceration observed in the two mouse lines, we performed bulk RNA sequencing (RNAseq) analysis on the proximal colons of 10-week-old A/D and B6D mice, with or without Ptges inactivation