Behavioural phenotypes of Dicer knockout in the mouse SCN

• Published in: The European journal of neuroscience Vol. 60; no. 11; pp. 6634 - 6651
• Main Authors: Du, Ngoc‐Hien, Kompotis, Konstantinos, Sato, Miho, Pedron, Erica, Androvic, Sabrina, Brown, Steven
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.12.2024; John Wiley and Sons Inc
• Subjects: Animals; Behavior, Animal - physiology; Circadian rhythm; Circadian Rhythm - genetics; Circadian Rhythm - physiology; Circadian rhythms; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Dicer knockout; Locomotor activity; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miRNAs; Motor Activity - physiology; Oscillations; period length; Phenotype; Phenotypes; Physiology; Ribonuclease III - genetics; Ribonuclease III - metabolism; SCN; Special Issue; SPECIAL ISSUE ARTICLE; Suprachiasmatic nucleus; Suprachiasmatic Nucleus - metabolism; Suprachiasmatic Nucleus - physiology; Ultradian rhythms; period length; locomotor activity; miRNAs; circadian rhythms; Dicer knockout; SCN
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.16605

The suprachiasmatic nucleus (SCN) is the master clock that directly dictates behavioural rhythms to 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. To study the behavioural consequences of miRNA depletion in the SCN, we first generated a mouse model in which Dicer is inactivated in the SCN by crossing Syt10Cre mice with Dicerflox mice to study behavioural consequences of miRNA depletion in the SCN. Loss of all mature miRNAs in the SCN shortened the circadian period length by ~37 minutes at the tissue level and by ~45 minutes at the locomotor activity level. Moreover, knockout animals exhibited a reduction in the precision of the circadian rhythm with more variable activity onsets under both LD 12:12 and DD conditions. We also observed that knockouts with higher onset variations were inclined to develop ultradian rhythms under constant light. In a second mouse model, recombination of Dicerflox via Cre delivery specifically in the SCN resulted in loss of behavioural rhythms in some animals depending on the injection efficiency. Together, our observations highlight the importance of microRNAs for a physiological SCN function and their pivotal role in robust circadian oscillations. We report here the behavioural phenotypes of conditional Dicer knockout in the suprachiasmatic nucleus. Both at tissue and organismal levels, clocks run faster when miRNAs are depleted in the master clock. Knockout mice also have less precise clocks as assessed by onset variations under both DD and LD. Finally, higher onset variations correlate with ultradian rhythms under LL in knockouts.