Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II

Nature. 1995 Nov 23;378(6555):406-9. doi: 10.1038/378406a0.


Prostaglandins have wide-ranging effects in the body and are thought to be important mediators of inflammation. Cyclooxygenase (COX) plays a key regulatory role in prostaglandin synthesis, and occurs in both constitutive (COX-1) and inducible (COX-2) isoforms. COX-1 is thought to provide cytoprotective effects, whereas COX-2 is both inducible and the major isoform of inflammatory cells. Reduction of prostaglandin production by inhibition of cyclooxygenases appears to be the main mechanism of action of most non-steroidal anti-inflammatory drugs (NSAIDS). Here we present an animal model of COX-2 deficiency that was generated by gene targeting. Defects in null mice correlating with reduced viability included renal alterations, characteristic of renal dysplasia (100% penetrance), and cardiac fibrosis (50% penetrance). Female Cox-2-/- mice were infertile. COX-2 deficiency failed to alter inflammatory responses in several standard models, but striking mitigation of endotoxin-induced hepatocellular cytotoxicity was observed.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cell Line
  • Cyclooxygenase Inhibitors
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Gene Targeting
  • Heart Diseases / enzymology
  • Heart Diseases / genetics
  • Infertility, Female / enzymology
  • Infertility, Female / genetics
  • Inflammation / enzymology*
  • Inflammation / genetics
  • Kidney / abnormalities*
  • Kidney / embryology
  • Kidney / enzymology
  • Liver / embryology
  • Liver / enzymology
  • Mice
  • Mice, Knockout
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / physiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Prostaglandin-Endoperoxide Synthases