In vivo patterns of heme oxygenase-1 transcription.
Gene fusions composed of specific promoters and bioluminescent reporter genes can be used to assess gene expression patterns using whole-body imaging in living animal models. A transgenic mouse model was developed using the regulatory elements of the heme oxygenase promoter to drive luciferase as the reporter gene. In these transgenic mice, heme oxygenase (HO)-1 expression was apparent in neuronal tissues of neonates but not adults as measured by whole-body imaging, and in adults transcription of the reporter gene was inducible by known inducers of HO-1 transcription. Whole-body imaging of luciferase activity was then used to evaluate the effects of metalloporphyrins (Mps) on the transcription of the reporter gene. Some of the Mps, which are potent inhibitors of HO activity, did not activate the reporter gene above background. These Mps are ideally suited as chemotherapeutics that may target bilirubin production rates by inhibiting HO activity, but not result in a net increase in output from the HO gene. In contrast, known inducers of HO transcription did increase luciferase activity as did some of the other Mps that have been examined. Using whole-body in vivo transcriptional assays may facilitate rapid screening of potential therapeutic compounds for both desired and untoward effects.
Contag
C H
CH
Division of Neonatal and Developmental Medicine, Department of Pediatrics, S230 Grant Building, Stanford University Medical Center, Stanford, CA 94305-5208, USA.
Stevenson
D K
DK
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017930:Genes, Reporter; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D008156:Luciferases; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse