Mouse Model--targeted Gene Knock-out Of Prostaglandin Sy

Environmental Health Sciences

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Abstract

Summary of Work: Mice deficient in both COX-1 and COX-2 have been produced. These mice are being used to determine the physiological roles of the individual COX isoforms and to elucidate the ways in which the two isoforms act individually or in conjunction. Mice deficient in both isoforms die shortly after birth of patent ductus arteriosus, but otherwise appear developmentally normal. We have found that COX-2 is the isoform primarily responsible for the closure of the ductus and that COX-2, but not COX-1, is induced in the contracting smooth mucles of the ductus. In further studies, we have demonstrated that COX-1 or COX-2 selective inhibitors duplicate the results obtained with the COC knockout mice.