Whole brain transcriptome analysis of PTEN C-terminus mutant mice

PTEN contains a C-terminal motif that binds to various PDZ domain-containing proteins including PSD-95. The PTEN C-terminus is known to mediate synaptic translocation of PTEN during long-term depression (LTD) and amyloid-b-induced synaptic depression. However, it remains unknown whether it regulates other synaptic functions. We compared the transcriptomic profiles of WT and PTEN C-terminus mutant brains (male) at P21. Here, we report genes that are differentially regulated in the mutant mice. This RNA-Seq analysis revealed a total of nine major differentially expressed genes (DEGs) –three upregulated and six downregulated (P < 0.05). Further gene set enrichment analysis (GSEA) of PTEN C-terminus mutant and WT transcriptomes using 5917 gene sets in the C5 (gene ontology) category revealed two strongly enriched gene ontology functions: ribosome biogenesis (positive) and transmembrane transport (negative). Our results provide a comprehensive transcriptome characterization of PTEN C-terminus mutant mice, which would provide a framework of understanding the role PTEN c-terminus in mediating various synaptic –and in larger sense, cellular –functions, and also allow thorough comparative analysis with the results of other PTEN mutant mouse lines. Overall design: Whole brain transcriptome of P21 wild-type and PTEN C-terminus mutant mice.

PTEN含有一段C端基序，可与包括PSD-95在内的多种含PDZ结构域的蛋白质结合。已知PTEN的C端可在长时程抑制（LTD）以及淀粉样β蛋白诱导的突触抑制过程中介导PTEN的突触转位。然而，其是否调控其他突触功能仍未明确。本研究对比了出生后第21天（P21）的雄性野生型（Wild Type, WT）与PTEN C端突变小鼠的全脑转录组谱，报道了突变小鼠中存在差异调控的基因。本次RNA测序（RNA-Seq）分析共鉴定出9个主要的差异表达基因（Differentially Expressed Genes, DEGs），其中3个上调、6个下调（P < 0.05）。后续我们使用C5（基因本体，Gene Ontology）类别下的5917个基因集，对PTEN C端突变小鼠与野生型小鼠的转录组进行基因集富集分析（Gene Set Enrichment Analysis, GSEA），结果显示两个显著富集的基因本体功能条目：核糖体生物发生（正向富集）与跨膜运输（负向富集）。本研究的结果全面表征了PTEN C端突变小鼠的转录组，可为理解PTEN C端介导各类突触功能——更广泛而言，细胞功能——的作用提供研究框架，同时也为与其他PTEN突变小鼠品系的研究结果开展全面对比分析提供基础。实验整体设计：取出生后第21天的野生型与PTEN C端突变小鼠的全脑进行转录组分析。