Deletion of the miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 locus enhances anxiety-related behaviour.
Hum. Mol. Genet.. 2016-01-06; 25(4): 728-739
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1. Hum Mol Genet. 2016 Feb 15;25(4):728-39. doi: 10.1093/hmg/ddv510. Epub 2016 Jan
Deletion of the miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 locus
enhances anxiety-related behaviour.
Marty V(1), Labialle S(1), Bortolin-Cavaillé ML(1), Ferreira De Medeiros G(2),
Moisan MP(2), Florian C(3), Cavaillé J(4).
(1)Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, UPS and
CNRS, LBME, F-31000 Toulouse, France.
(2)INRA, Nutrition and Integrative Neurobiology, Bordeaux, France, University of
Bordeaux, Bordeaux, France.
(3)Centre de Recherches sur la Cognition Animale, Université de Toulouse, UPS and
Centre de Recherches sur la Cognition Animale, CNRS, UMR 5169, 118 route de
Narbonne, F-31062 Toulouse cedex 9, France.
(4)Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse, UPS and
CNRS, LBME, F-31000 Toulouse, France, .
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.
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PMID: 26744330 [Indexed for MEDLINE]