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Behavioral phenotypes of SCN-specific Dicer knockout mice
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  • Ngoc-Hien Du,
  • Konstantinos Kompotis,
  • Miho Sato,
  • Steven Brown
Ngoc-Hien Du
University of Zurich

Corresponding Author:[email protected]

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Konstantinos Kompotis
University of Zurich
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Miho Sato
University of Zurich
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Steven Brown
University of Zurich
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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.
29 Mar 2024Submitted to European Journal of Neuroscience
31 Mar 2024Review(s) Completed, Editorial Evaluation Pending
26 Jul 20241st Revision Received
09 Aug 2024Submission Checks Completed
09 Aug 2024Assigned to Editor
09 Aug 2024Review(s) Completed, Editorial Evaluation Pending
09 Aug 2024Reviewer(s) Assigned
16 Sep 2024Editorial Decision: Revise Major
15 Oct 20242nd Revision Received
17 Oct 2024Review(s) Completed, Editorial Evaluation Pending
17 Oct 2024Submission Checks Completed
17 Oct 2024Assigned to Editor
18 Oct 2024Reviewer(s) Assigned
29 Oct 2024Editorial Decision: Accept