Contains a disruption of the Ptgs2 gene, one of the prostaglandin endoperoxide synthase/cyclooxygenase genes, preventing synthesis of cyclooxygenase-2 (COX-2) protein
COX-1 and COX-2 are key cyclooxygenase isoforms that catalyze key steps in the prostaglandin synthesis
Non-steroidal anti-inflammatory drugs (NSAIDs) target COX isoforms to inhibit them as a primary means of reducing inflammation
Unlike COX-1, COX-2 is normally undetectable in most tissues; inflammatory stimuli can induce macrophages and other migratory cells to synthesize it
Homozygotes exhibit normal inflammatory response to bacterial assault and to arachidonic acid and other inflammatory agents
Although survival of weaned animals is normal, homozygous mice develop peritoneal lesion and exhibit severe, progressive renal pathology, and lesions of varying severity that cause a progressive deterioration with aging
Useful to examine the redundant and compensatory responses of the cyclooxygenase gene, to study cyclooxygenase inhibitors and NSAIDs, to examine the role of COX enzymes in inflammatory disease, and to study the role of COX enzymes in pregnancy and parturition
Genetic Background: C57BL/6, 129P2 Mixed Background
The COX-2 mouse was developed in the laboratories of Robert Langenbach at NIEHS and Oliver Smithies at University of North Carolina in 1995 . The model was created by targeting the Ptgs2 gene in E14TG2a embryonic stem cells derived from 129P2/OlaHsd mice and injecting the targeted cells into C57BL/6J blastocysts. Resultant chimeras were backcrossed to C57BL/6J mice. Taconic received stock in September 1998 for embryo transfer derivation into the NIEHS repository. The model was transferred from NIEHS to Taconic in 2002 and derived by embryo transfer. The line was maintained on a mixed B6;129P2 background by breeding homozygous males to heterozygous females. A separate wild type colony was also maintained.
Wild type for Nnt mutation
Morham SG. Langenbach R, Loftin CD, Tiano HF, Vouloumanos N, Jennette JC, Mahler JF, Kluckman KD, Ledford A, Lee CA, Smithies O. (1995) Prostaglandin Synthase 2 Gene Disruption Causes Severe Renal Pathology in the Mouse. Cell, 83(3):472-482.