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

T Ishikawa, NK Jain, MM Taketo… - Molecular Imaging and …, 2006 - Springer
T Ishikawa, NK Jain, MM Taketo, HR Herschman
Molecular Imaging and Biology, 2006Springer
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 …
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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