PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues

Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5339-46. doi: 10.1073/pnas.0308709101. Epub 2004 Feb 12.

Abstract

Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), and current dogma holds that the SCN is required for the expression of circadian rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a real-time reporter of circadian dynamics in mice, we report that, contrary to previous work, peripheral tissues are capable of self-sustained circadian oscillations for >20 cycles in isolation. In addition, peripheral organs expressed tissue-specific differences in circadian period and phase. Surprisingly, lesions of the SCN in mPer2(Luciferase) knockin mice did not abolish circadian rhythms in peripheral tissues, but instead caused phase desynchrony among the tissues of individual animals and from animal to animal. These results demonstrate that peripheral tissues express self-sustained, rather than damped, circadian oscillations and suggest the existence of organ-specific synchronizers of circadian rhythms at the cell and tissue level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Cornea / physiology
  • Culture Techniques
  • Female
  • Kidney / physiology
  • Liver / physiology
  • Luciferases / genetics*
  • Luciferases / metabolism
  • Luminescent Measurements
  • Lung / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phenotype
  • Pituitary Gland / physiology
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / physiology
  • Suprachiasmatic Nucleus / physiology

Substances

  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Luciferases