Wild-derived mice: from genetic diversity to variation in immune responses.
Wild-derived mice: from genetic diversity to variation in immune responses.
复制标题
野生小鼠：从遗传多样性到免疫反应的变化。
DOI：
10.1007/s00335-018-9766-3
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Sherbak,Sergei
中科院分区：
文献类型：
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作者：
Poltorak,Alexander;Apalko,Svetlana;Sherbak,Sergei
经典的近交系小鼠品系在历史上一直有助于映射免疫性状。然而，大多数经典菌株起源于数量相对有限的创始动物，主要是家鼠亚种。因此，它们的遗传多样性最终是有限的。因此，使用这些小鼠进行免疫信号传导途径的详尽询问是不可行的。为了通过正向遗传分析研究网络，需要比实验室条件下引入的更大的遗传多样性。最近，建立了来自其他小鼠亚种的近交系，如Mus musculus castaneus和Mus musculus musculus，它们在一百多万年前与Mus musculus domesticus有一个共同的祖先。一个直接的基因组比较清楚地表明，野生衍生的小鼠和经典的近交系之间发生的进化分歧。当与经典的近交系小鼠相比时，野生小鼠每100-200个碱基对就表现出多态性。研究这些特征的分子基础为我们提供了深入了解免疫系统如何进化调节功能以适应环境特异性约束的机会。由于大多数野生来源的品系能够与经典的近交系小鼠繁殖，它们代表了向前遗传研究的进化上显著多样性的丰富来源。这些生物体是一个新兴的，但在很大程度上还未开发，用于识别和研究新的免疫基因的模型。
Classical inbred mouse strains have historically been instrumental in mapping immunological traits. However, most of the classical strains originate from a relatively limited number of founder animals, largely within theMus musculus domesticussubspecies. Therefore, their genetic diversity is ultimately limited. For this reason, it is not feasible to use these mice for exhaustive interrogation of immune signaling pathways. In order to investigate networks through forward genetic analysis, larger genetic diversity is required than is introduced under laboratory conditions. Recently, inbred strains from other mouse subspecies were established such asMus musculus castaneusandMus musculus musculus, which diverged from a shared common ancestor withMus musculus domesticusmore than one million years ago. A direct genomic comparison clearly demonstrates the evolutionary divergence that has occurred between wild-derived mice and the classical inbred strains. When compared to classical inbred strains, wild-derived mice exhibit polymorphisms every 100–200 base pairs. Studying the molecular basis of these traits provides us with insight into how the immune system can evolve regulatory features to accommodate environment-specific constraints. Because most wild-derived strains are able to breed with classical inbred mice, they represent a rich source of evolutionarily significant diversity for forward genetic studies. These organisms are an emerging, though still largely unexplored, model for the identification and study of novel immunological genes.