Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate

Angew Chem Int Ed Engl. 2019 Jun 11;58(24):7972-7976. doi: 10.1002/anie.201903058. Epub 2019 Apr 30.

Abstract

Microglia, the brain-resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure-activity relationships study, we developed CDr20, a high-performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome-scale CRISPR-Cas9 knockout screen, the UDP-glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence.

Keywords: biological activity; fluorescent probes; imaging agents; microglia; structure-activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • Glucuronosyltransferase / chemistry
  • Glucuronosyltransferase / metabolism
  • Mice
  • Microglia / chemistry*
  • Microglia / cytology*
  • Microglia / enzymology
  • Optical Imaging / methods

Substances

  • Fluorescent Dyes
  • Glucuronosyltransferase