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Imaging Cyclooxygenase-2 (Cox-2) Gene Expression in Living Animals with a Luciferase Knock-in Reporter Gene

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Abstract

The cyclooxygenase-2 (Cox-2) gene plays a role in a variety of normal and pathophysiological conditions. Expression of the Cox-2 gene is induced in a broad range of cells, in response to many distinct stimuli. The ability to monitor and quantify Cox-2 expression noninvasively in vivo may facilitate a better understanding of the role of Cox-2, both in normal physiology and in different diseases. We generated a “knock-in” mouse in which the firefly luciferase reporter enzyme is expressed at the start site of translation of the endogenous Cox-2 gene. Correlation of luciferase and Cox-2 expression was confirmed in heterozygous Cox-2 luc/+ mouse embryonic fibroblasts isolated from the knock-in mouse. In an acute sepsis model, following injection of interferon gamma and endotoxin, ex vivo imaging and Western blotting demonstrated coordinate Cox-2 and luciferase induction in multiple organs. Using both paw and air pouch inflammation models, we can monitor repeatedly localized luciferase expression in the same living mouse. Cox-2 luc/+ knock-in mice should provide a valuable tool to analyze Cox-2 expression in many disease models.

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Acknowledgments

We thank Art Catapang and Raymond Bascontillo for technical assistance, Masanobu Oshima for genomic fragments, Alex Garcia and Hong Wu for assistance with immunohistochemistry and immunofluorescence, and Shankkar Pattabhiraman and Hong Wu for helpful discussions and comments. We also acknowledge the important assistance of the UCLA Jonsson Comprehensive Cancer Center Shared Resource for embryonic stem cell homologous recombination, and for transgenic/knockout mouse production. These studies were supported by grants R01 CA84572 and P50 CA86306 (H.R.H., principal investigator).

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  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, 341 Boyer Hall, 611 Charles E. Young Drive East, UCLA, Los Angeles, CA, 90095, USA

    Tomo-o Ishikawa, Naveen K. Jain & Harvey R. Herschman PhD

  2. Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Tomo-o Ishikawa & Makoto M. Taketo

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  1. Tomo-o Ishikawa
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Correspondence to Harvey R. Herschman PhD.

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Ishikawa, To., Jain, N.K., Taketo, M.M. et al. Imaging Cyclooxygenase-2 (Cox-2) Gene Expression in Living Animals with a Luciferase Knock-in Reporter Gene. Mol Imaging Biol 8, 171–187 (2006). https://doi.org/10.1007/s11307-006-0034-7

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