Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse.
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.
Department of Pathology, University of North Carolina at Chapel Hill 27599-7525, USA.
S G
SG
Morham
R
R
Langenbach
C D
CD
Loftin
H F
HF
Tiano
N
N
Vouloumanos
J C
JC
Jennette
J F
JF
Mahler
K D
KD
Kluckman
A
A
Ledford
C A
CA
Lee
O
O
Smithies
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D007668:Kidney / Q000201:enzymology / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009026:Mortality; D010032:Otitis Externa / Q000139:chemically induced; D010537:Peritoneum / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate