A novel genetic model of selective COX-2 inhibition: comparison with COX-2 null mice.
Prostaglandin H Synthase (PGHS) is a bi-functional enzyme with a cyclooxygenase (COX) activity and a functionally linked peroxidase (POX) activity that exists in two isoforms (COX-1, COX-2). Non-steroidal anti-inflammatory drugs (NSAIDs), including the selective COX-2 inhibitors, block COX activity while leaving POX activity unscathed. Recently, some selective COX-2 inhibitors were withdrawn from the market due to elevated cardiovascular risk in placebo-controlled trials. Mice deficient for PGHS2 were developed in 1995 and through numerous subsequent studies have revealed significant roles in renal development, ductus arteriosus patency/closure, skin carcinogenesis and cardiovascular function. In this short review, we compare a novel genetic COX-2 selective inhibition mouse model with the originally described COX-2 null mice in these different physiological functions.
Yu
Ying
Y
Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Funk
Colin D
CD
D019943:Amino Acid Substitution; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010544:Peroxidases / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced
D052246:Cyclooxygenase 2 Inhibitors; C022464:prostaglandin hydroperoxidase; D010544:Peroxidases; D051546:Cyclooxygenase 2