In vivo imaging of clock gene expression in multiple tissues of freely moving mice

Nat Commun. 2016 Jun 10;7:11705. doi: 10.1038/ncomms11705.


Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1(-/-) Cry2(-/-) arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CLOCK Proteins / genetics*
  • CLOCK Proteins / metabolism
  • Circadian Rhythm / genetics
  • Circadian Rhythm / radiation effects
  • Firefly Luciferin / metabolism
  • Gene Expression Regulation* / radiation effects
  • Light
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Imaging*
  • Movement*
  • Organ Specificity / genetics*


  • Firefly Luciferin
  • CLOCK Proteins