不同声音刺激易感性的基因表达谱：两种近交系实验鼠脑干的比较研究。
Gene expression profile for different susceptibilities to sound stimulation: a comparative study on brainstems between two inbred laboratory mouse strains.
机构信息
Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Lane 37 #, Chengdu, 610041, Sichuan, China.
出版信息
BMC Genomics. 2022 Nov 30;23(1):783. doi: 10.1186/s12864-022-09016-3.
BACKGROUND
DBA/1 mice have a higher susceptibility to generalized audiogenic seizures (AGSz) and seizure-induced respiratory arrest (S-IRA) than C57/BL6 mice. The gene expression profile might be potentially related to this difference. This study aimed to investigate the susceptibility difference in AGSz and S-IRA between DBA/1 and C57BL/6 mice by profiling long noncoding RNAs (lncRNAs) and mRNA expression.
METHODS
We compared lncRNAs and mRNAs from the brainstem of the two strains with Arraystar Mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD). Gene Ontology (GO) and pathway analyses were performed to determine the potentially related biological functions and pathways based on differentially expressed mRNAs. qRT-PCR was carried out to validate the results.
RESULTS
A total of 897 lncRNAs and 438 mRNAs were differentially expressed (fold change ≥2, P < 0.05), of which 192 lncRNAs were upregulated and 705 lncRNAs were downregulated. A total of 138 mRNAs were upregulated, and 300 mRNAs were downregulated. In terms of specific mRNAs, Htr5b, Gabra2, Hspa1b and Gfra1 may be related to AGSz or S-IRA. Additionally, lncRNA Neat1 may participate in the difference in susceptibility. GO and pathway analyses suggested that TGF-β signaling, metabolic process and MHC protein complex could be involved in these differences. Coexpression analysis identified 9 differentially expressed antisense lncRNAs and 115 long intergenic noncoding RNAs (lincRNAs), and 2010012P19Rik and its adjacent RNA Tnfsf12-Tnfsf13 may have participated in S-IRA by regulating sympathetic neuron function. The results of the qRT-PCR of five selected lncRNAs (AK038711, Gm11762, 1500004A13Rik, AA388235 and Neat1) and four selected mRNAs (Hspa1b, Htr5b, Gabra2 and Gfra1) were consistent with those obtained by microarray.
CONCLUSION
We concluded that TGF-β signaling and metabolic process may contribute to the differential sensitivity to AGSz and S-IRA. Among mRNAs, Htr5b, Gabra2, Hspa1b and Gfra1 could potentially influence the susceptibility. LncRNA Neat1 and 2010012P19Rik may also contribute to the different response to sound stimulation. Further studies should be carried out to explore the underlying functions and mechanisms of differentially expressed RNAs.
背景
DBA/1 小鼠比 C57/BL6 小鼠更容易发生全身听觉性癫痫发作（AGSz）和癫痫诱导性呼吸暂停（S-IRA）。基因表达谱可能与这种差异有关。本研究旨在通过分析长非编码 RNA（lncRNA）和 mRNA 表达，研究 DBA/1 和 C57BL/6 小鼠在 AGSz 和 S-IRA 中的易感性差异。
方法
我们使用 Arraystar Mouse lncRNA Microarray V3.0（Arraystar，马里兰州罗克维尔）比较了两种品系脑干中的 lncRNA 和 mRNA。根据差异表达的 mRNA，进行基因本体论（GO）和通路分析，以确定潜在相关的生物学功能和通路。进行 qRT-PCR 验证。
结果
总共鉴定出 897 个差异表达的 lncRNA（fold change≥2，P<0.05）和 438 个差异表达的 mRNA，其中 192 个 lncRNA 上调，705 个 lncRNA 下调。138 个 mRNA 上调，300 个 mRNA 下调。在特定的 mRNA 中，Htr5b、Gabra2、Hspa1b 和 Gfra1 可能与 AGSz 或 S-IRA 有关。此外，lncRNA Neat1 可能参与了易感性的差异。GO 和通路分析表明，TGF-β 信号、代谢过程和 MHC 蛋白复合物可能参与其中。共表达分析鉴定出 9 个差异表达的反义 lncRNA 和 115 个长非编码 RNA（lincRNA），2010012P19Rik 及其相邻 RNA Tnfsf12-Tnfsf13 可能通过调节交感神经元功能参与 S-IRA。5 个选定的 lncRNA（AK038711、Gm11762、1500004A13Rik、AA388235 和 Neat1）和 4 个选定的 mRNA（Hspa1b、Htr5b、Gabra2 和 Gfra1）的 qRT-PCR 结果与微阵列结果一致。
结论
我们得出结论，TGF-β 信号和代谢过程可能有助于 AGSz 和 S-IRA 的敏感性差异。在 mRNA 中，Htr5b、Gabra2、Hspa1b 和 Gfra1 可能潜在地影响易感性。lncRNA Neat1 和 2010012P19Rik 也可能有助于对声音刺激的不同反应。应进一步研究以探索差异表达 RNA 的潜在功能和机制。
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