Abstract
The suprachiasmatic nucleus (SCN) is the master clock that orchestrates
circadian clocks across the body to synchronize with and anticipate the
earth’s light/dark cycles. Although post-transcriptional regulators
called microRNAs have been implicated in physiological SCN function, how
the absence of the entire mature miRNome impacts SCN output has not yet
been explored. Here, we have generated an SCN-specific Dicer knockout
mouse model by crossing Syt10Cre mice with Dicerflox mice to study
behavioral consequences of miRNA depletion in the SCN. We show that loss
of all mature miRNAs in the SCN shortens the circadian period length by
~40 minutes at the tissue level, and by ~50
minutes at the locomotor activity level. Knockout animals also showed
arrythmicity or ultradian locomotor activities with no light masking
under constant light, a condition which usually caused lengthening of
the circadian period length and reduced activities, i.e. light masking,
in nocturnal animals. Moreover, induction of Dicer knockout by Cre
injection into the SCN of adult Dicerflox mice eventually resulted in
loss of behavioral rhythms. Finally, we show suggestive evidence that
SCN desynchronization might be one mechanism underlying the behavioral
phenotypes of SCN-specific Dicer knockout animals.