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In vivo expression patterns of heme oxygenase-1 gene in transgenic mice Weisheng Zhang*1; PR Contag1; HJ Vreman2; DK Stevenson2; CH Contag2 (1) 860 Atlantic Avenue, Alameda, CA 94501, USA; (2) Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University Medical Center, Stanford University, Stanford, CA 94305      *(wzhang@xenogen.com) Assessing gene function in transgenic animals would be enhanced by rapid, noninvasive functional assays. We used luciferase imaging as a functional screen to identify bioluminescent transgenic mice where the transgene consisted of the heme oxygenase-1 (HO-1) promoter fused to the luciferase gene. The light production from these transgenic mice indicated that the desired DNA fragment was integrated and functional. Luciferase assays demonstrated the inducibility of the HO-1 promoter in response to known inducers such as as CdCl2 and heme. HO enzymes are rate-limiting in heme degradation, and account, in part, for elevated bilirubin in neonatal hyprbilirubinemia. Competitive inhibitors of HO, have been studied for the prevention of hyperbilirubinemia. However, many of these compounds increase transcription of HO-1, which may reduce their utility. Using in vivo imaging, three HO inhibitors were evaluated in transgenic mice, and whole body imaging revealed differential effects on HO-1 expression, demonstrating that spatiotemporal analyses of transcriptional regulation in living animals can accelerate the analyses of potential therapeutics. [Poster: zhang.weishe.40022]

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