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.
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