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.
Morham
S G
SG
Department of Pathology, University of North Carolina at Chapel Hill 27599-7525, USA.
Langenbach
R
R
Loftin
C D
CD
Tiano
H F
HF
Vouloumanos
N
N
Jennette
J C
JC
Mahler
J F
JF
Kluckman
K D
KD
Ledford
A
A
Lee
C A
CA
Smithies
O
O
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