Wellcome Trust Centre for Gene Regulation, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
PLoS One. 2013 Apr 26;8(4):e62509. doi: 10.1371/journal.pone.0062509. Print 2013.
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.
miR-132 和 miR-212 是两个密切相关的 miRNA，它们编码在一个小非编码基因的同一个内含子中，被认为在免疫和神经元功能中都发挥作用。我们在这里描述了 miR-132/212 双敲除小鼠的产生和初步特征。这些小鼠具有活力和繁殖力，没有明显的不良表型。对先天免疫反应的分析，包括 TLR 诱导的细胞因子产生和对原代成纤维细胞病毒感染的 IFNβ诱导，在敲除鼠中没有发现任何表型。相比之下，miR-132 和 miR-212 的缺失虽然没有明显影响神经元形态，但确实影响了突触功能。在海马和新皮层切片中，miR-132/212 敲除小鼠降低了基础突触传递，而不影响成对脉冲易化。由强直刺激诱导的海马长时程增强（LTP）不受 miR-132/212 缺失的影响，而θ爆发 LTP 则增强。相反，皮质θ爆发诱导的 LTP 被 miR-132/212 的缺失抑制。这些结果表明，miR-132 和/或 miR-212 在突触功能中发挥重要作用，可能通过调节基础条件下和活动依赖性突触可塑性期间的突触后 AMPA 受体数量。
