Genetic deletion of the inflammatory bowel disease-associated risk gene Rgs14 aggravates experimental colitis

Regulators of G protein signaling (RGS) deactivate G proteins associated with G protein-coupled receptors (GPCRs), a large receptor family with diverse functions. Of the 20 RGS, the Rgs14 single-nucleotide polymorphism is associated with inflammatory bowel disease, and Rgs14 expression is higher in macrophages than in epithelial cells. This manuscript describes a novel conditional mouse line that enables deletion of Rgs14 in macrophages and intestinal epithelial cells. We demonstrate that Rgs14 deletion in macrophages increases their reactive oxygen species production and their ability to induce T cell proliferation. The deletion in macrophages, but not in epithelial cells, exacerbates colitis severity. This novel conditional mouse model will facilitate further investigation of Rgs14 in inflammatory bowel disease and potentially in other areas, including metabolism, neuroscience, and aging.