RNA-seq analysis dataset: Cerebellum tissues from wild type and Dscam del17/del17 mice at P21
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The cytoplasmic domain of DSCAM has been reported to exhibit transcriptional activity on genes involved in neuronal wiring in HEK293 cells. Thus, we addressed the possibility that deregulation of the CF synapse in Dscamdel17/del17 mice is caused by the reduced expression of CF synaptogenesis-related genes, by using RNA-seq analyses using the P21 whole cerebellum of WT and Dscamdel17/del17 mice. Expression levels of most of the genes, except for Nefl, Mal, Fat2, and Fat1, were not significantly different between the WT and Dscamdel17/del17 mice, probably because depletion of Dscam in the cerebellum affects only a few cell types, including Purkinje cells. We also confirmed the unchanged expression of Purkinje cell-specific genes (and their encoded proteins), such as Cacna1a (Cav2.1), Sema7a and Sema3a, Grm1 (mGluR1) and Prkcg (protein kinase gamma [PKCgamma]), Grid2 (GluD2), and Adgrb3 (Bai3) between the WT and Dscamdel17/del17 mice. These results raise the possibility that DSCAM in Purkinje cells regulates synapse formation and function, independently of the regulation of gene expression of known CF synaptogenesis-related genes. The mRNA profiles of the cerebellum tissues from five Dscamdel17/del17 homozygous mutant mice and five control mice at P21 were generated using the Illumina NovaSeq platform.
已有研究报道,唐氏综合征细胞黏附分子(DSCAM)的胞质结构域在人胚肾293(HEK293)细胞中可对参与神经元回路构建的基因发挥转录调控活性。据此,本研究针对Dscamdel17/del17小鼠的攀缘纤维(Climbing Fiber, CF)突触失调是否由CF突触发生相关基因表达下调所引发这一科学问题展开探究,采用RNA测序(RNA-seq)技术对出生后21天(P21)的野生型(WT)及Dscamdel17/del17小鼠的全小脑组织进行转录组分析。结果显示,除Nefl、Mal、Fat2及Fat1外,绝大多数基因在野生型与Dscamdel17/del17小鼠间的表达水平无显著差异,这一现象可能源于小脑内DSCAM的缺失仅影响少数细胞类型,其中包括浦肯野细胞(Purkinje cells)。本研究同时证实,野生型与Dscamdel17/del17小鼠的小脑组织中,浦肯野细胞特异性基因及其编码蛋白的表达均未发生明显改变,相关基因包括Cacna1a(Cav2.1)、Sema7a、Sema3a、Grm1(代谢型谷氨酸受体1,mGluR1)、Prkcg(蛋白激酶γ[PKCγ])、Grid2(谷氨酸受体δ2,GluD2)以及Adgrb3(Bai3)。上述结果提示,浦肯野细胞中的DSCAM可独立于已知CF突触发生相关基因的表达调控过程,参与突触形成与功能调节。本研究采用Illumina NovaSeq测序平台,对5只P21天龄的Dscamdel17/del17纯合突变小鼠及5只同批次对照小鼠的小脑组织进行mRNA测序,成功获取了其转录组表达谱。




