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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021179-10
Application #
6681841
Study Section
(LECM)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Aid, Saba; Langenbach, Robert; Bosetti, Francesca (2008) Neuroinflammatory response to lipopolysaccharide is exacerbated in mice genetically deficient in cyclooxygenase-2. J Neuroinflammation 5:17
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Salvatore, Michael F; Fisher, Brent; Surgener, Stewart P et al. (2005) Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Brain Res Mol Brain Res 139:341-7

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