Abstract
Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti-inflammatory drugs. To study the physiological roles of the individual isoforms, we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type. The homozygous mutant mice have reduced platelet aggregation and a decreased inflammatory response to arachidonic acid, but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated to homozygous mutant males produce few live offspring. COX-1-deficient mice provide a useful model to distinguish the physiological roles of COX-1 and COX-2.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
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Arachidonic Acid / adverse effects*
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Blotting, Northern
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Blotting, Western
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Cloning, Molecular
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Dinoprostone / biosynthesis
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Female
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Gastritis / chemically induced
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Gastritis / genetics*
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Genetic Vectors / genetics*
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Homozygote
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Indomethacin / pharmacology*
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Macrophages, Peritoneal / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mutation / physiology
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Otitis Externa / chemically induced
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Phenotype
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Plasmids / genetics
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Platelet Aggregation / physiology
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Prostaglandin-Endoperoxide Synthases / drug effects
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Prostaglandin-Endoperoxide Synthases / genetics*
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Stomach Ulcer / chemically induced
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Stomach Ulcer / genetics*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Arachidonic Acid
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone
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Indomethacin