动物模型被广泛的应用在心血管疾病的研究中，然而，利用这些动物模型进行实验，通常会发生实验结果达不到预期目标或者大相径庭。
在构建与发展人类疾病动物模型过程中，最根本的问题是要清楚疾病基因在模式动物中的功能保守性。
为了深入探讨人类心血管疾病动物模型与人之间的差异，在中国科学院昆明动物研究所生物信息与系统生物学实验室黄京飞研究员的指导下，博士生赵玉琪与盛自章等对人类以及四种心血管疾病动物模型（（小鼠，大鼠，猕猴，狗）的转录组进行了全面细致的比较。研究发现，尽管大部分基因受到强烈的负选择，但是有一些通路在动物模型与人间发生了分化。并且，不同的动物模型与人之间发生分化的通路不尽相同。共表达网络结果还显示，基因的表达演化并不是单独发生的，而是通过形成模块共同演化的。这项研究为更好的发展心血管疾病模型以及研究基因表达的演化提供了有力的数据及方法学支持。
该研究目前已在线发表于Molecular BioSystems。该工作得到国家自然基金和云南省自然基金等的大力支持。（生物谷 Bioon）
doi:10.1039/C1MB05415E
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A systematic analysis of heart transcriptome highlights divergent cardiovascular disease pathways between animal models and humans.
Yuqi Zhao , Zizhang Sheng and Jingfei Huang
Animal models have been extensively used in the study of cardiovascular disease (CVD) and have provided important insights into disease pathogenesis and drug development. However, the level of conservation of gene expression patterns of the orthologous genes between human and animal models was unclear. To address this issue, we compared the expression of orthologous genes in human and four models (rhesus, rat, mouse and dog), based on 42 normal heart samples with high quality gene expression data. The results show that the global expression profiles between animal model and human orthologous genes are highly preserved. The phylogenetic tree inferred from the gene expression profiles has similar topology to that of the species tree. However, differentially expressed genes (DEGs) between human and each model were identified and these four gene datasets are enriched with different molecular functions, including hormone-receptor binding and geranyl transferase activity. The 65 overlapped DEGs between four sets are involved in thyroid cancer, proteasome systems, aminoacyl-tRNA biosynthesis and GST (Glycine, Serine and Threonine) metabolism, of which functions are divergent between models and humans. In addition, 46.2% (30/65) of the communal genes have been experimentally proven to be associated with cardiovascular disease. Next, we constructed a co-expression network based on intra- and inter-species variation, to elucidate the altered network organization. It indicates that these DEGs evolved as modules rather than independently. The integrated heart transcriptome data should provide a valuable resource for the in-depth understanding of cardiology and the development of cardiovascular disease models.
