THE DBP GENE IS EXPRESSED ACCORDING TO A CIRCADIAN-RHYTHM IN THE SUPRACHIASMATIC NUCLEUS AND INFLUENCES CIRCADIAN BEHAVIOR

DBP, a PAR leucine zipper transcription factor, accumulates according to a robust circadian rhythm in liver and several other tissues of mou se and rat. Here we report that DBP mRNA levels also oscillate strongl y in the suprachiasmatic nucleus (SCN) of the hypothalamus, believed t o harbor the central mammalian pacemaker. However, peak and minimum le vels of DBP mRNA are reached about 4 h earlier in the SCN than in live r, suggesting that circadian DBP expression is controlled by different mechanisms in SCN and in peripheral tissues. Mice homozygous for a DB P-null allele display less locomotor activity and free-run with a shor ter period than otherwise isogenic wild-type animals, The altered loco motor activity in DBP mutant mice and the highly rhythmic expression o f the DBP gene in SCN neurons suggest that DBP is involved in controll ing 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 ou tput pathway than a master gene of the clock.