Objective

To compare the transcriptional differences between the T2DM-susceptible and T2DM-tolerant Bama mini-pigs and to determine the utility of Bama mini-pigs as an animal model for T2DM by comparing the transcriptomes of the animals with T2DM patients.

Methods

The skeletal muscle transcriptomes of healthy Guangxi Bama mini-pigs (CON), T2DM pigs (T2D), and non-T2DM pigs (NT2D) were determined by RNA sequencing.

Results

A total of 290 differentially expressed genes (DEGs) were detected in NT2D relative to the CON groups, 572 DEGs in T2D compared to CON, and 300 DEGs in T2D compared to NT2D. The RNA-seq data was verified by qPCR analysis of PGC1α, NR4A3, CSRP3, MYH7, MYH2, MYH1, GLUT4, PPARγ, LEP, ATP5H, UCP2, and MTOR transcripts. The DEGs in T2D Bama mini-pigs were mainly involved in signaling pathways associated with metabolism, cardiovascular diseases, infectious disease, cancer, inflammation and immune responses, cytoskeleton, and signal transduction. Comparative analysis of the transcriptomes of T2DM Bama mini-pigs and T2DM patients (GSE29221 dataset) revealed 17 differentially co-expressed genes that were assigned to 11 GO terms and 6 annotated pathways, including hypertrophic cardiomyopathy, dilated cardiomyopathy, thyroid cancer, cardiac muscle contraction, tight junction, and calcium signaling pathway, suggesting that the T2D Bama mini-pigs could be used on T2DM research in those pathways.

Conclusion

This study represents the first RNAseq transcriptome analysis in T2D Bama mini-pigs and provided a new perspective for the study on the human T2DM pathogenesis by using the T2DM model of Bama mini-pigs.

中文翻译：

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T2DM巴马小型猪与T2DM患者转录组的比较分析

客观的

比较 T2DM 易感和 T2DM 耐受的巴马小型猪之间的转录差异，并通过比较动物与 T2DM 患者的转录组来确定巴马小型猪作为 T2DM 动物模型的效用。

方法

通过RNA测序确定健康广西巴马小型猪（CON）、T2DM猪（T2D）和非T2DM猪（NT2D）的骨骼肌转录组。

结果

相对于 CON 组，在 NT2D 中检测到总共 290 个差异表达基因 (DEG)，与 CON 相比，T2D 中检测到 572 个差异表达基因 (DEG)，与 NT2D 相比，T2D 中检测到 300 个差异表达基因。RNA-seq 数据通过PGC1α、NR4A3、CSRP3、MYH7、MYH2、MYH1、GLUT4、PPARγ、LEP、ATP5H、UCP2和MTOR 的qPCR 分析验证成绩单。T2D巴马小型猪中的DEGs主要参与与代谢、心血管疾病、传染病、癌症、炎症和免疫反应、细胞骨架和信号转导相关的信号通路。T2DM 巴马小型猪和 T2DM 患者转录组的比较分析（GSE29221 数据集）揭示了 17 个差异共表达基因，这些基因被分配到 11 个 GO 术语和 6 个注释通路，包括肥厚型心肌病、扩张型心肌病、甲状腺癌、心肌收缩、紧密连接和钙信号通路，表明 T2D 巴马小型猪可用于这些通路中的 T2DM 研究。

结论

该研究代表了T2D巴马小型猪的首次RNAseq转录组分析，为利用巴马小型猪的T2DM模型研究人类T2DM发病机制提供了新的视角。