Ptger4-flox Mouse

Ptger4, the prostaglandin E2 receptor 4, is crucial for maintaining gut homeostasis. It is involved in various biological processes, with its activation by prostaglandin E2 (PGE2) leading to downstream signaling that impacts cell differentiation, proliferation, and gene expression. The receptor is associated with pathways such as mitogen-activated protein kinases (MAPKs) and is of great importance in inflammation resolution, mucosal healing, and stem-cell regulation [1,2].

In Csf1r-iCre Ptger4fl/fl mice (a conditional knockout, CKO, mouse model), defective mucosal healing and epithelial barrier regeneration were observed in a model of dextran sulfate sodium (DSS)-induced colitis. This indicates that PTGER4-expressing intestinal macrophages are essential for supporting the intestinal stem cell niche and the regeneration of the injured epithelium. Mechanistically, PGE2-induced CXCL1 secretion in PTGER4+ macrophages via MAPKs drives epithelial cell differentiation and proliferation during colitis [1].

In epithelial-specific Ptger4-ablated mutant mice, the regenerative reprogramming of stem cells was misdirected, preventing Sca-1+ cell expansion and sporadic tumour initiation, demonstrating the paracrine control of tumour-initiating stem cells by PGE2-Ptger4 [3].

In conclusion, Ptger4 is essential for gut-related biological functions like mucosal healing and stem-cell regulation. Studies using gene knockout (KO) and CKO mouse models have revealed its significant role in inflammatory bowel disease and colorectal cancer, providing insights into potential therapeutic targets for these diseases.