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

Scott G. Morham, Robert Langenbach, Charles D. Loftin, Howard F. Tiano, Nectarios Vouloumanos, J. Charles Jennette, Joel F. Mahler, Kimberly D. Kluckman, Aric Ledford, Christopher A. Lee, Oliver Smithies

Research output: Contribution to journalArticlepeer-review

1033 Scopus citations


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.

Original languageEnglish
Pages (from-to)473-482
Number of pages10
Issue number3
StatePublished - Nov 3 1995

Bibliographical note

Funding Information:
We thank S. Bronson, D. Cook, S. Kirby, J. Krege, R. Kucherlapati, N. Maeda, and L. Marnett for review of the manuscript. We thank D. Lee, A. Staton, G. O’Neal, and Y. Zhou for invaluable technical assistance. We also appreciate the efforts of B. Gaul for necropsy assistance, as well as the efforts of the National Institute of Environmental Health Sciences histology lab. This work was supported by grants GM20069 and HL49227 from the National Institutes of Health to 0. S.; S. G. M. is an American Cancer Society fellow (#PF-3973). We gratefully acknowledge a grant from the W. M. Keck Foundation to the University of North Carolina to support work with animal models.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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