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

Abstract

PROSTAGLANDINS have wide-ranging effects in the body and are thought to be important mediators of inflammation. Cyclooxygen-ase (COX) plays a key regulatory role in prostaglandin synthesis, and occurs in both constitutive (COX-1) and inducible (COX-2) isoforms1,2. COX-1 is thought to provide cytoprotective effects3, whereas COX-2 is both inducible and the major isoform of inflammatory cells4. Reduction of prostaglandin production by inhibition of cyclooxygenases appears to be the main mechanism of action of most non-steroidal anti-inflammatory drugs (NSAIDS)5. 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.

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Dinchuk, J., Car, B., Focht, R. et al. Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 378, 406–409 (1995). https://doi.org/10.1038/378406a0

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