The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states using the COX deficient mice. Included in these studies are the roles of the COX isoforms in gastric ulceration, inflammation and in kidney and cardiovascular development. Aside from our early studies in gastric ulceration, inflammation and kidney development in COX deficient mice most of our more recent studies on these topics have been through collaborative efforts and will not be described here. The major effort within the laboratory has been to develop COX-1-COX-2 double deficient mice and to study cardiovascular development in these mice. Mice deficient in both COX-1 and COX-2 have been produced and these mice, as well as mice carrying only a single functional copy of one of the COX genes have been developed and studied. Mice deficient in both isoforms die shortly after birth of patent ductus arteriosus (DA), 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 muscles of the DA as it closes. Thus functional COX-2, and not COX-1, is needed for ductus closure. Studies with COX-1 and COX-2 selective inhibitors have been used and are in agreement, and extend, the data obtained with the genetically deficient COX mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021179-11
Application #
6837373
Study Section
(LECM)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2003
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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