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

Nature volume 378, pages 406–409 (1995)Cite this article

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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Author notes

  1. Joseph E. Dinchuk and Richard J. Focht: The DuPont Merck Pharmaceutical Company, Glenolden,Pennsylvania 19036-2307, USA

  2. Vicki M. Eng: University Laboratory Animal Resources, University of Pennsylvania,Philadelphia, Pennsylvania 19104-6021, USA

Authors and Affiliations

  1. The DuPont Merck Pharmaceutical Company, Wilmington, Delaware, 19880-0400, USA

    Joseph E. Dinchuk, Bruce D. Car, Richard J. Focht, Jennifer J. Johnston, Bruce D. Jaffee, Maryanne B. Covington, Nancy R. Contel, Vicki M. Eng, Robert J. Collins, Philip M. Czerniak, Stewart A. Gorry & James M. Trzaskos

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  1. Joseph E. Dinchuk
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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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