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| The EMBO Journal
(1997) 16, 6762–6771, doi:10.1093/emboj/16.22.6762 |
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| The DBP gene is expressed according to a circadian rhythm in the suprachiasmatic nucleus and influences circadian behavior |
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| Luis Lopez-Molina1, François Conquet2, Michel Dubois-Dauphin3 and Ueli Schibler1 |
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1 Département de Biologie Moléculaire, Sciences II, Université de Genève, 30, Quai Ernest Ansermet, CH-1211 Genève-4, Switzerland 2 Glaxo–Wellcome Research and Development SA, Genève Switzerland 3 HUG Belle Idée, Division de Neuropsychiatrie, Genève, Switzerland Received 1 August 1997. |
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| Abstract |
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| DBP, a PAR leucine zipper transcription factor, accumulates according to a robust circadian rhythm in liver and several other tissues of mouse and rat. Here we report that DBP mRNA levels also oscillate strongly in the suprachiasmatic nucleus (SCN) of the hypothalamus, believed to harbor the central mammalian pacemaker. However, peak and minimum levels of DBP mRNA are reached about 4 h earlier in the SCN than in liver, suggesting that circadian DBP expression is controlled by different mechanisms in SCN and in peripheral tissues. Mice homozygous for a DBP-null allele display less locomotor activity and free-run with a shorter period than otherwise isogenic wild-type animals. The altered locomotor activity in DBP mutant mice and the highly rhythmic expression of the DBP gene in SCN neurons suggest that DBP is involved in controlling circadian behavior. However, since DBP-/- mice are still rhythmic and since DBP protein is not required for the circadian expression of its own gene, dbp is more likely to be a component of the circadian output pathway than a master gene of the clock. |
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| Keywords: circadian behavior, DBP, PAR leucine zipper proteins, suprachiasmatic nucleus, transcription factor |
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