Sex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specific Egr1 loss.
Sex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specific Egr1 loss.
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DOI：
10.3389/fnins.2023.1240209
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发表时间：
2023
影响因子：
4.3
通讯作者：
Xie, Hehuang
中科院分区：
文献类型：
--
作者：
Swilley, Cody;Lin, Yu;Zheng, Yuze;Xu, Xiguang;Liu, Min;Jarome, Timothy;Hodes, Georgia E.;Xie, Hehuang
转录因子EGR1在许多神经过程中起着重要作用，包括学习和记忆以及对压力的反应。Egr1完全敲除小鼠表现出抑郁或焦虑样行为减少，空间学习和记忆表现受损。然而，Egr1在不同细胞类型中的具体功能在很大程度上尚未得到充分研究。在这项研究中，我们编目了nesting - cre介导的Egr1条件敲除（Egr1cKO）小鼠及其对照组的行为和转录组学特征。尽管条件敲除没有改变伤害性或焦虑反应，但它引发了焦虑测试期间女性探索性活动的变化。在物体定位任务中，海马体依赖的空间学习不受影响，但雌性Egr1cKO小鼠在情境恐惧条件反射任务测试中确实表现出比雄性小鼠更差的记忆力。RNA-seq数据分析显示，单独存在固定的Egr1盒或nesting - cre驱动程序对海马基因表达有微妙的影响。在nesting - cre介导的Egr1条件敲除小鼠中，性别相关差异被放大，雌性小鼠对Egr1基因的缺失更敏感。神经元细胞系中Egr1缺失导致的差异表达基因与Wnt信号通路、细胞外基质和轴突引导的调控显著相关。总之，我们的研究结果表明，神经元细胞系中nesting - cre和Egr1的缺失以性别特异性的方式对海马基因表达有明显的影响。
The transcription factor EGR1 is instrumental in numerous neurological processes, encompassing learning and memory as well as the reaction to stress. Egr1 complete knockout mice demonstrate decreased depressive or anxiety-like behavior and impaired performance in spatial learning and memory. Nevertheless, the specific functions of Egr1 in distinct cell types have been largely underexplored. In this study, we cataloged the behavioral and transcriptomic character of Nestin-Cre mediated Egr1 conditional knockout (Egr1cKO) mice together with their controls. Although the conditional knockout did not change nociceptive or anxiety responses, it triggered changes in female exploratory activity during anxiety testing. Hippocampus-dependent spatial learning in the object location task was unaffected, but female Egr1cKO mice did exhibit poorer retention during testing on a contextual fear conditioning task compared to males. RNA-seq data analyses revealed that the presence of the floxed Egr1 cassette or Nestin-Cre driver alone exerts a subtle influence on hippocampal gene expression. The sex-related differences were amplified in Nestin-Cre mediated Egr1 conditional knockout mice and female mice are more sensitive to the loss of Egr1 gene. Differentially expressed genes resulted from the loss of Egr1 in neuronal cell lineage were significantly associated with the regulation of Wnt signaling pathway, extracellular matrix, and axon guidance. Altogether, our results demonstrate that Nestin-Cre and the loss of Egr1 in neuronal cell lineage have distinct impacts on hippocampal gene expression in a sex-specific manner.
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