Genomic responses in mouse models poorly mimic human inflammatory diseases
Genomic responses in mouse models poorly mimic human inflammatory diseases
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DOI：
10.1073/pnas.1222878110
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发表时间：
2013-02-26
影响因子：
11.1
通讯作者：
Tompkins, Ronald G.
中科院分区：
文献类型：
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作者：
Seok, Junhee;Warren, H. Shaw;Tompkins, Ronald G.
现代生物医学研究的一个基石是使用小鼠模型来探索基本的病理生理机制，评估新的治疗方法，并做出通过或不通过的决定，将新药候选推进临床试验。目前还没有系统的研究来评估小鼠模型模拟人类炎症性疾病的程度。在这里，我们表明，尽管来自不同病因的急性炎症应激在人类中导致高度相似的基因组反应，但相应的小鼠模型中的反应与人类条件以及彼此之间的相关性很差。在人类显著变化的基因中，小鼠的同源基因在匹配人类同源基因方面几乎是随机的(例如，R-2介于0.0和0.1之间)。除了改进目前的动物模型系统外，我们的研究还支持将转化医学研究的重点放在更复杂的人类状况上，而不是依赖小鼠模型来研究人类炎症性疾病。
A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R-2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.