叶亚龙, 朱莉芳, 高林辉, 龚玲, 何苗
Analysis of miR-34a function in brain development and behavior using knockout mouse model
YE Ya-Long, ZHU Li-Fang, GAO Lin-Hui, GONG Ling, HE Miao
Institutes of Brain Science, Fudan University, Shanghai 200032, China
miR-34a is a conserved microRNA highly expressed in the brain. It is thought to play critical roles in regulating many aspects of brain development and function, such as neural stem cell proliferation and differentiation, neuronal migration and apoptosis, fear memory consolidation, etc. However, the assessment of its function was mainly conducted through vector-mediated overexpression and miRNA sponge or antagomir-mediated functional suppression, therefore may suffer from nonspecific off-target effects or incomplete inactivation. We thus analyzed mouse model with a targeted deletion of miR-34a which completely abolishes its expression. To our surprise, loss of miR-34a led to neither an obvious change in brain size, morphology or cortical lamination, nor impaired marker gene expression in major excitatory and inhibitory neuron types in the neocortex. In addition, miR-34a ablation did not affect fear memory formation or consolidation, as well as the anxiety or depression related behavior. However, the performance of mice in rotarod assay was significantly affected, suggesting a defect in motor activity in miR-34a deficient mice. As neocortical parvalbumin (PV) neurons are known for high level miR-34a expression, we also tested the effect of PV-Cre-mediated conditional miR-34a deletion. Similar as germline deletion, PV neuron specific miR-34a deletion did not affect cortical lamination or PV expression in the neocortex. Our studies suggest that, although miR-34a may be involved in regulating certain aspects of brain development or function, such as motor activity, it does not play a significant role in regulating brain morphogenesis, cortical lamination or neocortical neuron subtype specification, and it is also dispensable for fear memory formation, expression and consolidation.
通讯作者：何苗 E-mail: email@example.com
叶亚龙, 朱莉芳, 高林辉, 龚玲, 何苗. miR-34a敲除对小鼠大脑发育和行为的影响[J]. 生理学报 2017; 69 (4): 452-460.
YE Ya-Long, ZHU Li-Fang, GAO Lin-Hui, GONG Ling, HE Miao. Analysis of miR-34a function in brain development and behavior using knockout mouse model. Acta Physiol Sin 2017; 69 (4): 452-460 (in Chinese with English abstract).