| Summary: | <p>Abstract</p> <p>Background</p> <p>Circadian organisation of behavioural and physiological rhythms in mammals is largely driven by the clock in the suprachiasmatic nuclei (SCN) of the hypothalamus. In this clock, a molecular transcriptional repression and activation mechanism generates near 24 hour rhythms. One of the outputs of the molecular clock in specific SCN neurons is arginine-vasopressin (AVP), which is responsive to transcriptional activation by clock gene products. As negative regulators, the protein products of the <it>period </it>genes are thought to repress transcriptional activity of the positive limb after heterodimerisation with CRYPTOCHROME. When both the <it>Per1 </it>and <it>Per2 </it>genes are dysfunctional by targeted deletion of the PAS heterodimer binding domain, mice lose circadian organization of behaviour upon release into constant environmental conditions. To which degree the period genes are involved in the control of AVP output is unknown.</p> <p>Methods</p> <p>Using an <it>in vitro </it>slice culture setup, SCN-AVP release of cultures made of 10 wildtype and 9 <it>Per1/2 </it>double-mutant mice was assayed. Mice were sacrificed in either the early light phase of the light-dark cycle, or in the early subjective day on the first day of constant dark.</p> <p>Results</p> <p>Here we report that in arrhythmic homozygous <it>Per1/2 </it>double-mutant mice there is still a diurnal peak in <it>in vitro </it>AVP release from the SCN similar to that of wildtypes but distinctively different from the release pattern from the paraventricular nucleus. Such a modulation of AVP release is unexpected in mice where the circadian clockwork is thought to be disrupted.</p> <p>Conclusion</p> <p>Our results suggest that the circadian clock in these animals, although deficient in (most) behavioural and molecular rhythms, may still be (partially) functional, possibly as an hourglass mechanism. The level of perturbation of the clock in <it>Per1/2 </it>double mutants may therefore be less than was originally thought.</p>
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