MOUSE MODEL--TARGETED GENE KNOCK-OUT OF PROSTAGLANDIN SYNTHASE I AND II

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Summary of Work: A series of projects to elucidate the physiological functions of the individual cyclooxygenase (COX) isoforms are ongoing with the COX knockout mice. 1) Tumorigenesis in the COX1 and COX2 null strains has been studied using the DMBA/TPA two stage skin model and the Apc (min) mutant mice. Tumor formation was reduced by 75% in both COX1 and COX2 deficient mice compared to the controls in both of these tumorigenesis models. This appears to be due to alterations in several homeostatic factors, including cell replication, differentiation and apoptosis. 2) Effects on transplantable tumor growth in the COX null mice are being studied using injectable B16-F1 cells. Tumor size and onset are reduced somewhat in the COX1 null mice and substantially in the COX2 null mice. 3) Mice deficient in both COX1 and COX2 have been produced. These mice, and mice carrying only a single copy of one of the COX genes, are being used to determine the physiological roles of the individual COX isoforms. Mice deficient in both isoforms die shortly after birth of patent ductus arteriosus. In addition, developmental defects in several internal organs are observed. - cyclooxygenase, cox, ptgs, colon, skin, prostaglandin, tumorigenesis