Sentrin/SUMO-specific protease 2 (SENP2) is a member of SENPs family involved in maturation of SUMO precursors and deSUMOylation of specific target, and is highly expressed in the central nervous system (CNS). Although SENP2 has been shown to modulate embryonic development, fatty acid metabolism, atherosclerosis and epilepsy, the function of SENP2 in the CNS remains poorly understood. To address the role of SENP2 in the CNS and its potential involvement in neuropathology, we generated SENP2 conditional knockout mice by crossing floxed SENP2 mice with CaMKIIα-Cre transgenic mice. Behavioral tests revealed that SENP2 ablation induced hyper-locomotor activity, anxiolytic-like behaviors, spatial working memory impairment and fear-associated learning defect. In line with these observations, our RNA sequencing (RNA-seq) data identified a variety of differential expression genes that are particularly enriched in locomotion, learning and memory related biologic process. Taken together, our results indicated that SENP2 plays a critical role in emotional and cognitive regulation. This SENP2 conditional knockout mice model may help reveal novel mechanisms that underlie a variety of neuropsychiatric disorders associated with anxiety and cognition.

中文翻译：

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前脑兴奋性神经元特异性SENP2基因敲除小鼠表现出过度活跃，学习和记忆受损以及抗焦虑样行为。

Sentrin / SUMO特异性蛋白酶2（SENP2）是SENPs家族的成员，参与SUMO前体的成熟和特定靶标的去SUMOylation，并在中枢神经系统（CNS）中高度表达。尽管SENP2已被证明可调节胚胎发育，脂肪酸代谢，动脉粥样硬化和癫痫病，但SENP2在中枢神经系统中的功能仍知之甚少。为了解决SENP2在中枢神经系统中的作用及其在神经病理学中的潜在作用，我们通过将浮雕的SENP2小鼠与CaMKIIα-Cre转基因小鼠杂交，产生了SENP2条件性基因敲除小鼠。行为测试表明，SENP2消融诱导了过度运动能力活动，抗焦虑样行为，空间工作记忆障碍和与恐惧相关的学习缺陷。根据这些观察，我们的RNA测序（RNA-seq）数据确定了多种差异表达基因，这些基因在与运动，学习和记忆有关的生物过程中特别丰富。综上所述，我们的结果表明SENP2在情绪和认知调节中起关键作用。这种SENP2条件性基因敲除小鼠模型可能有助于揭示新机制，这些机制是与焦虑和认知有关的多种神经精神疾病的基础。