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Proceedings Paper

Functional imaging: monitoring heme oxygenase-1 gene expression in vivo
Author(s): Weisheng Zhang; Pamela Reilly-Contag; David K. Stevenson; Christopher H. Contag
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Paper Abstract

The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

Paper Details

Date Published: 2 July 1999
PDF: 6 pages
Proc. SPIE 3600, Biomedical Imaging: Reporters, Dyes, and Instrumentation, (2 July 1999); doi: 10.1117/12.351022
Show Author Affiliations
Weisheng Zhang, Stanford Univ. School of Medicine (United States)
Pamela Reilly-Contag, Xenogen Corp. (United States)
David K. Stevenson, Stanford Univ. School of Medicine (United States)
Christopher H. Contag, Stanford Univ. School of Medicine (United States)

Published in SPIE Proceedings Vol. 3600:
Biomedical Imaging: Reporters, Dyes, and Instrumentation
Eva Marie Sevick-Muraca; Darryl J. Bornhop; Christopher H. Contag; Eva Marie Sevick-Muraca, Editor(s)

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