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Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

机译：小鼠中PEA-15的缺失与空间学习能力的特定损伤有关

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Background PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. Results We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. Conclusion We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.
机译：背景PEA-15是一种结合并调节ERK MAP激酶和RSK2的磷蛋白，并在整个大脑中高度表达。由于这些相互作用，PEA-15改变了c-Fos和CREB介导的转录。为了确定PEA-15是否有助于神经系统的功能，我们在旨在测量学习，感觉/运动功能和应激反应性的一系列实验中测试了缺少PEA-15的小鼠。结果我们报告PEA-15空小鼠在三个不同的空间任务中表现出学习障碍，而它们表现出正常的恐惧条件，被动回避，以自我为中心的导航和气味识别。 PEA-15无效小鼠还具有不足的前爪强度，并且在有限的情况下，应激反应性和/或焦虑性增强。但是，这些非认知变量似乎并未解决观察到的空间学习障碍。与野生型对照相比，空小鼠维持正常体重，疼痛敏感性和协调性。结论我们发现PEA-15空小鼠的空间学习障碍与ERK或RSK2功能受损的小鼠相似。我们建议PEA-15可能是依赖ERK的空间学习的重要调节剂。

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