The tissue-specific, compensatory expression of cyclooxygenase-1 and -2 in transgenic mice.
Prostaglandins are essential regulators of tissue homeostasis, reproduction and inflammation. We have recently shown that cells derived from cyclooxygenase (COX)-deficient mice express higher, compensatory levels of the remaining COX isozyme [Kirtikara et al., J. Exp. Med., 187, 517 (1998)]. To assess this compensatory expression phenomenon in vivo, we quantified COX-1 and COX-2 mRNA levels in various organs of COX-1- and COX-2-ablated mice using a reverse transcriptase-polymerase chain reaction (RT-PCR) method. We found that COX-1 and COX-2 mRNAs in the brains of COX-ablated mice were elevated > 2-fold compared with wild-type (WT) animals. COX-2 mRNA was enhanced approximately 2-fold in the kidneys and stomachs of COX-1-deficient mice while COX-1 expression remained unchanged. Conversely, the livers of COX-2-deficient mice expressed 15-fold higher COX-1 mRNA levels, while hepatic COX-2 mRNA levels were not significantly altered in the COX-1-ablated mice. Steady state levels of COX-1 and COX-2 mRNAs in the hearts, lungs and spleens of WT, COX-1- and COX-2-deficient mice were indistinguishable from each other. Peritoneal macrophages isolated from COX-1- and COX-2-ablated mice also expressed significantly higher steady-state levels of cytoplasmic phospholipase A2 and 5-lipooxygenase mRNAs suggesting a global upregulation of eicosanoid biosynthetic pathways in COX-deficient mice. These data suggest that expression of both COX-1 and COX-2 can be re-programmed to compensate for the lack of both alleles of the alternate COX gene in transgenic mice.
Zhang
Jianyi
J
Department of Veterans Affairs Medical Center, Memphis, TN 38104, USA.
Goorha
Sarita
S
Raghow
Rajendra
R
Ballou
Leslie R
LR
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D017353:Gene Deletion; D020869:Gene Expression Profiling; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010741:Phospholipases A; D054467:Phospholipases A2