Cushman Jesse, Lo Jeannette, Huang Zhi, Wasserfall Clive, Petitto John M
Department of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Clin Diagn Lab Immunol. 2003 Jan;10(1):13-8. doi: 10.1128/cdli.10.1.13-18.2003.
Recombinase activation gene 1 (RAG-1) function is essential for V(D)J recombination in T-cell-receptor and immunoglobulin rearrangements whereby the immune system may encode memories of a vast array of antigens. The RAG-1 gene is also localized to neurons in the hippocampal formation and related limbic regions that are involved in spatial learning and memory as well as other parameters of neurobehavioral performance. Since the unique ability to encode memory is shared by the immune system and the brain, we tested the hypothesis that loss of the RAG-1 gene in the brain would influence learning and memory performance and examined several different domains of behavior in RAG-1-knockout and control mice. Compared to control mice, RAG-1-knockout mice exhibited increased locomotor activity in an open field under both dim and bright lighting conditions and decreased habituation (reduction in the expected decline in locomotor activity with increasing familiarity with the novel environment in a 1-h test session) in bright lighting. RAG-1-knockout mice also showed reduced levels of fearfulness for some measures of fear-motivated behavior in both the open-field behavior test and elevated-plus maze test. Contrary to our hypothesis, no differences in spatial learning and memory were found between the groups, although modest differences were observed visible-platform testing in the Morris water maze. Neither prepulse inhibition, a measure of sensorimotor gating, nor reflexive acoustic startle responses differed between the RAG-1-knockout and control mice. It remains to be determined if these changes are due to the loss of RAG-1 gene expression in the brain, are due to the absence of the gene in the immune system (e.g., the loss of cytokines with neuromodulatory activities), or are due to some combination of both effects. Study of the neurobiological actions of RAG-1 in the brain may provide new insights into important processes involved in normal brain function and disease.
重组激活基因1（RAG-1）的功能对于T细胞受体和免疫球蛋白重排中的V（D）J重组至关重要，免疫系统由此能够编码对大量抗原的记忆。RAG-1基因也定位于海马结构及相关边缘区域的神经元中，这些区域参与空间学习和记忆以及神经行为表现的其他参数。由于免疫系统和大脑都具有编码记忆的独特能力，我们测试了如下假设：大脑中RAG-1基因的缺失会影响学习和记忆表现，并在RAG-1基因敲除小鼠和对照小鼠中检查了几个不同的行为领域。与对照小鼠相比，RAG-1基因敲除小鼠在暗光和亮光条件下的旷场实验中均表现出运动活性增加，且在亮光条件下习惯化程度降低（在1小时测试过程中，随着对新环境熟悉程度增加，运动活性预期下降的幅度减小）。在旷场行为测试和高架十字迷宫测试中，RAG-1基因敲除小鼠在某些恐惧驱动行为指标上也表现出恐惧水平降低。与我们的假设相反，尽管在莫里斯水迷宫的可见平台测试中观察到了适度差异，但两组之间在空间学习和记忆方面未发现差异。RAG-1基因敲除小鼠和对照小鼠在感觉运动门控指标前脉冲抑制以及反射性听觉惊吓反应方面均无差异。这些变化是由于大脑中RAG-1基因表达缺失、免疫系统中该基因缺失（例如，具有神经调节活性的细胞因子缺失）还是两者共同作用的某种组合，仍有待确定。对大脑中RAG-1神经生物学作用的研究可能会为正常脑功能和疾病所涉及的重要过程提供新的见解。
