In 1995, two independent groups published the first data from global knockout (KO) strains of COX-2 [2, 3] and COX-1[4], showing that global knock out of COX-2 results in early development of kidney failure, spontaneous peritonitis, a substantial reduction of fetal survival related to failed closure of the ductus arteriosus, and several other severe defects, whereas global knock out of COX-1 renders generally healthy animals. Here, PTGS2 is linked to peritonitis.