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Chromosomal Organization of the Inducible and Constitutive Prostaglandin Synthase/Cyclooxygenase Genes in Mouse

1993; Elsevier BV; Volume: 15; Issue: 2 Linguagem: Inglês

10.1006/geno.1993.1091

1089-8646

Ping Wen, Craig H. Warden, Bradley S. Fletcher, Dean A. Kujubu, Harvey R. Herschman, Aldons J. Lusis,

Eicosanoids and Hypertension Pharmacology

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 ≈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.