Prostaglandin Synthase 1 Gene Disruption in Mice Reduces Arachidonic Acid-Induced Inflammation and Indomethacin-Induced Gastric Ulceration

Cell. 1995 Nov 3;83(3):483-92. doi: 10.1016/0092-8674(95)90126-4.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Arachidonic Acid / adverse effects*
  • Blotting, Northern
  • Blotting, Western
  • Cloning, Molecular
  • Dinoprostone / biosynthesis
  • Female
  • Gastritis / chemically induced
  • Gastritis / genetics*
  • Genetic Vectors / genetics*
  • Homozygote
  • Indomethacin / pharmacology*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation / physiology
  • Otitis Externa / chemically induced
  • Phenotype
  • Plasmids / genetics
  • Platelet Aggregation / physiology
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / genetics*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Arachidonic Acid
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Indomethacin