In order to study mechanisms of renal fibrosis, ADTKD-UMOD and ER stress due to uromodulin mutations relevant to ADTKD-UMOD in humans, we generated a targeted mouse knock-in model by homologous recombination in mouse embryonic stem (ES) cells, to produce mice carrying a known disease-causing mutation, Cys125Arg (C125R), within the mouse Umod gene. This evidence concerns the gene UMOD and renal fibrosis.