Deletion of the miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 locus enhances anxiety-related behaviour

• Published in: Human molecular genetics Vol. 25; no. 4; pp. 728 - 739
• Main Authors: Marty, Virginie, Labialle, Stéphane, Bortolin-Cavaillé, Marie-Line, Ferreira De Medeiros, Gabriela, Moisan, Marie-Pierre, Florian, Cédrick, Cavaillé, Jérôme
• Format: Journal Article
• Language: English
• Published: England Oxford University Press (OUP) 15.02.2016
• Subjects: Animals; Anxiety - genetics; Anxiety - metabolism; Behavior, Animal; Cognitive science; Female; Genomic Imprinting; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Iodide Peroxidase - genetics; Iodide Peroxidase - metabolism; Life Sciences; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Multigene Family; Sequence Deletion
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddv510

The brain-specific miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 domain is implicated in several aspects of brain development and function, particularly in fine-tuning the dendritic outgrowth and spine remodelling of hippocampal neurons. Whether it might influence behaviour and memory-related processes has not yet been explored at the whole organism level. We previously reported that constitutive deletion of the miR-379/miR-410 gene cluster affects metabolic adaptation in neonatal mice. Here, we examined the role of this cluster in adult brain functions by subjecting mice with the constitutive deletion to a battery of behavioural and cognitive tests. We found that the lack of miR-379/miR-410 expression is associated with abnormal emotional responses, as demonstrated by increased anxiety-related behaviour in unfamiliar environments. In contrast, spontaneous exploration, general locomotion, mood levels and sociability remained unaltered. Surprisingly, miR-379/miR-410-deficient mice also showed normal learning and spatial (or contextual) memory abilities in hippocampus-dependent tasks involving neuronal plasticity. Taken together, the imprinted miR-379/miR-410 gene cluster thus emerges as a novel regulator of the two main post-natal physiological processes previously associated with imprinted, protein-coding genes: behaviour and energy homeostasis.