Imaging cyclooxygenase-2 (Cox-2) gene expression in living animals with a luciferase knock-in reporter gene

Mol Imaging Biol. May-Jun 2006;8(3):171-87. doi: 10.1007/s11307-006-0034-7.

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-2luc/+ 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-2luc/+ knock-in mice should provide a valuable tool to analyze Cox-2 expression in many disease models.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzothiazoles / administration & dosage
  • Benzothiazoles / metabolism
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics*
  • Embryonic Stem Cells / enzymology
  • Fireflies / genetics
  • Gene Knock-In Techniques* / methods
  • Genes, Reporter*
  • Luciferases / biosynthesis
  • Luciferases / genetics*
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Zymosan / administration & dosage

Substances

  • Benzothiazoles
  • D-luciferin
  • Zymosan
  • Luciferases
  • Cyclooxygenase 2