LONG-TERM MONITORING OF CIRCADIAN-RHYTHMS IN C-FOS GENE-EXPRESSION FROM SUPRACHIASMATIC NUCLEUS CULTURES

Background: The AP-1 family of transcription factors has been implicat ed in the control of the expression of many genes in response to envir onmental signals. Previous studies have provided temporal profiles for c-fos expression by taking measurements from many animals at several points in time, but these studies provide limited information about dy namic changes in expression. Here, we have devised a method of continu ously measuring c-fos expression. Results: A transgenic mouse line exp ressing the human c-fos promoter linked to the firefly luciferase repo rter gene (fos/luc) was generated to continuously monitor c-fos gene e xpression. A second transgenic mouse line expressing luciferase under the control of the cytomegalovirus promoter (CMV/luc) served as a cont rol. Luminescence originating from identifiable brain regions was imag ed from fos/luc brain slice cultures. Expression of the fos/luc transg ene accurately reflected transcriptional responses of the endogenous c -fos gene. Dynamic changes in fos/luc expression in suprachiasmatic nu clei (SCN) explant cultures were monitored continuously, and luminesce nce showed almost 24 hour rhythms lasting up to five circadian cycles. In contrast, bioluminescence monitored from CMV/luc SCN explant cultu res was not rhythmic. Conclusion: The fos/luc transgenic mouse will be useful for long-term, non-invasive monitoring of c-fos transcriptiona l responses to the changing cellular environment. Circadian rhythms in c-fos expression can be monitored non-invasively in real time from th e SCN, clearly demonstrating that c-fos transcription is regulated by the circadian clock. (C) Current Biology Ltd ISSN 0960-9822.