Contains a disruption of the Ptgs1 gene, one of the prostaglandin endoperoxide synthase/cyclooxygenase genes, preventing synthesis of cyclooxygenase-1 (COX-1) 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
Mice develop normally, appear healthy and do not exhibit gross or microscopic gastric lesions
Dosing with indomethacin results in less gastric ulceration than wild type mice
Both male and female homozygotes are fertile, however crosses between homozygotes result in decreased pup survival
Homozygous mice have a significantly reduced inflammatory response to arachidonic acid, but not to other inflammatory agents
Useful 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 Background
The COX-1 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 Ptgs1 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
Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, Mahler JF, Lee CA, Goulding EH, Kluckman KD, Kim HS, Smithies O. (1995) Prostaglandin Synthase 1 Gene Disruption in Mice Reduces Arachidonic Acid-Induced Inflammation and Indomethacin-Induced Gastric Ulceration. Cell, 83(3):483-492.