Table_1_Phenotypic Resemblance to Neuropsychiatric Disorder and Altered mRNA Profiles in Cortex and Hippocampus Underlying IL15Rα Knockout.DOCX

BackgroundPrevious studies of the functions of IL15Rα have been limited to immune activities and skeletal muscle development. Immunological factors have been identified as one of the multiple causes of psychosis, and neurological symptoms have been described in IL15Rα knockout (KO) mice. Seeking to explore possible mechanisms for this in the IL15Rα–/– mouse brain, we analyzed gene expression patterns in the cortex and hippocampus using the RNA-seq technique.MethodsIL15Rα KO mice were generated and littermate wildtype (WT) mice were used as a control group. A Y-maze was used to assess behavior differences between the two groups. The cortex and hippocampus of 3-month-old male mice were prepared and RNA-seq and transcriptome analysis were performed by gene set enrichment analysis (GSEA).ResultsCompared with the WT group, IL15Rα KO animals showed higher speed in the novel arm and more entrance frequency in the old arm in the Y-maze experiment. GSEA indicated that 18 pathways were downregulated and 13 pathways upregulated in both cortex and hippocampus from the GO, KEGG, and Hallmark gene sets. The downregulated pathways formed three clusters: respiratory chain and electron transport, regulation of steroid process, and skeletal muscle development.ConclusionIL15Rα KO mice exhibit altered expression of multiple pathways, which could affect many functions of the brain. Lipid biosynthesis and metabolism in the central nervous system (CNS) should be investigated to provide insights into the effect of IL15Rα on psychosis in this murine model.

背景：既往关于IL15Rα功能的研究主要集中于免疫活动和骨骼肌发育。免疫因素已被确认为导致精神错乱的多种原因之一，而IL15Rα敲除（KO）小鼠的神经系统症状亦有所描述。为探讨IL15Rα–/–小鼠脑部可能的致病机制，本研究利用RNA测序技术分析了皮质和海马区基因表达模式。方法：构建了IL15Rα KO小鼠并选取其同窝野生型（WT）小鼠作为对照组。采用Y迷宫评估两组小鼠的行为差异。制备3个月龄雄性小鼠的皮质和海马区组织，并运用RNA测序及转录组学分析，通过基因集富集分析（GSEA）进行研究。结果：与WT组相比，IL15Rα KO小鼠在Y迷宫实验中新臂运动速度更快，旧臂进入频率更高。GSEA显示，GO、KEGG和Hallmark基因集均发现皮质和海马区存在18条下调通路和13条上调通路。下调通路可分为三个簇：呼吸链和电子传递、类固醇过程调控以及骨骼肌发育。结论：IL15Rα KO小鼠表现出多条通路表达的改变，这可能影响大脑的多种功能。中枢神经系统（CNS）中的脂质生物合成与代谢应被研究，以深入了解IL15Rα在本小鼠模型中对于精神错乱的影响。