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Photic and circadian expression of luciferase in mPeriod1-luc transgenic mice invivo

  1. Joseph S. Takahashi*
  1. *Howard Hughes Medical Institute, 2153 North Campus Drive, Northwestern University, Evanston, IL 60208; †Department of Biology, National Science Foundation Center for Biological Timing, P.O. Box 400328, University of Virginia, Charlottesville, VA 22904; and Departments of ‡Biology and §Mathematics, Washington University, St. Louis, MO 63130

  1. Edited by Steven L. McKnight, University of Texas Southwestern Medical Center, Dallas, TX, and approved October 24, 2001 (received for review May 17, 2001)

Abstract

A conserved transcription-translation negative feedback loop forms the molecular basis of the circadian oscillator in animals. Molecular interactions within this loop have been relatively well characterized in vitro and in cell culture; however, in vivo approaches are required to assess the functional significance of these interactions. Here, regulation of circadian gene expression was studied in vivo by using transgenic reporter mouse lines in which 6.75 kb of the mouse Period1 (mPer1) promoter drives luciferase (luc) expression. Six mPer1-luc transgenic lines were created, and all lines express a daily rhythm of luc mRNA in the suprachiasmatic nuclei (SCN). Each mPer1-luc line also sustains a long-term circadian rhythm of luminescence in SCN slice culture. A 6-h light pulse administered during the early subjective night rapidly induces luc mRNA expression in the SCN; however, high luc mRNA levels are sustained, whereas endogenous mPer1 mRNA levels return to baseline, suggesting that posttranscriptional events mediate the down-regulation of mPer1 after exposure to light. This approach demonstrates that the 6.75-kb mPer1 promoter fragment is sufficient to confer both circadian and photic regulation in vivo and reveals a potential posttranscriptional regulatory mechanism within the mammalian circadian oscillator.

Footnotes

    • ↵ To whom reprint requests should be addressed. E-mail: j-takahashi{at}northwestern.edu.

    • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviations

    SCN,
    suprachiasmatic nucleus/nuclei;
    P1L,
    mPer1-luc transgenic line;
    UTR,
    untranslated region;
    ZT,
    Zeitgeber time;
    CT,
    circadian time
    • Received May 17, 2001.

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