title: miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity.
abstract: miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity.
authors: Wellcome Trust Centre for Gene Regulation, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors: Judit
authors: J
authors: Remenyi
authors: Mirjam W M
authors: MW
authors: van den Bosch
authors: Oleg
authors: O
authors: Palygin
authors: Rajen B
authors: RB
authors: Mistry
authors: Colin
authors: C
authors: McKenzie
authors: Andrew
authors: A
authors: Macdonald
authors: Gyorgy
authors: G
authors: Hutvagner
authors: J Simon C
authors: JS
authors: Arthur
authors: Bruno G
authors: BG
authors: Frenguelli
authors: Yuriy
authors: Y
authors: Pankratov
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D061251:Primary Cell Culture; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D029082:Sendai virus / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: C546976:MIRN132 microRNA, mouse; C554518:MIRN212 microRNA, mouse; D035683:MicroRNAs; D018091:Receptors, AMPA; D016899:Interferon-beta
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