Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse

• Published in: Cell Vol. 83; no. 3; pp. 473 - 482
• Main Authors: Morham, Scott G., Langenbach, Robert, Loftin, Charles D., Tiano, Howard F., Vouloumanos, Nectarios, Jennette, J.Charles, Mahler, Joel F., Kluckman, Kimberly D., Ledford, Aric, Lee, Christopher A., Smithies, Oliver
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.11.1995
• Subjects: Animals; Arachidonic Acid - pharmacology; Bacteriophage lambda - genetics; Base Sequence; Dinoprostone - biosynthesis; Female; Genetic Vectors - genetics; Genotype; Homozygote; Kidney - enzymology; Kidney - pathology; Lipopolysaccharides - pharmacology; Macrophages, Peritoneal - metabolism; Male; Mice; Mice, Mutant Strains; Molecular Sequence Data; Mortality; Otitis Externa - chemically induced; Peritoneum - pathology; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(95)90125-6

The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is induced at high levels in migratory and other responding cells by pro-inflammatory stimuli. COX-2 is generally considered to be a mediator of inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and is thought to mediate “housekeeping” functions. These two enzymes are therapeutic targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To investigate further the different physiologic roles of these isoforms, we have used homologous recombination to disrupt the mouse gene encoding COX-2 ( Ptgs2). Mice lacking COX-2 have normal inflammatory responses to treatments with tetradecanoyl phorbol acetate or with arachidonic acid. However, they develop severe nephropathy and are susceptible to peritonitis.