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

Cell. 1995 Nov 3;83(3):473-82. doi: 10.1016/0092-8674(95)90125-6.


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.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acid / pharmacology
  • Bacteriophage lambda / genetics
  • Base Sequence
  • Dinoprostone / biosynthesis
  • Female
  • Genetic Vectors / genetics*
  • Genotype
  • Homozygote
  • Kidney / enzymology
  • Kidney / pathology*
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mortality
  • Otitis Externa / chemically induced
  • Peritoneum / pathology
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology


  • Lipopolysaccharides
  • Arachidonic Acid
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate