A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis).
A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis).
复制标题
在田鼠（Microtus agrestis）自然群体中鉴定出的候选耐受基因。
DOI：
10.1111/mec.14476
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发表时间：
2018
影响因子：
4.9
通讯作者：
Wanelik KM
中科院分区：
文献类型：
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作者：
Wanelik KM
迄今为止，动物免疫应答主要仅在抗性的背景下被观察。然而，面对持续的感染，个人也可以采用耐受策略来保持良好的健康。为了阐明耐受性的遗传和生理基础，我们使用自然种群的田鼠，田鼠，寻找转录因子Gata 3的表达之间的关联，以前确定为该系统中的耐受性标记，和多态性在84个免疫和非免疫基因。我们的研究结果表明，Gata 3表达和Fcer 1a基因多态性之间存在关联，这种多态性的解释力与以前确定为Gata 3表达重要预测因子的其他非遗传变量相当。我们还发现了这种关联背后的可能机制，使用现有的蛋白质-蛋白质相互作用网络的小鼠模型啮齿动物，小家鼠，我们验证使用我们自己的表达网络forM。Agrestis。我们的研究结果表明，所讨论的多态性可能在转录水平上起作用，导致Th 2相关基因，酪氨酸蛋白激酶BTK和酪氨酸蛋白激酶TXK表达的变化，因此可能改变Th 2反应的强度，其中Gata 3是介导者。我们相信我们的工作对传染病的治疗和控制都有意义。
The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals can also employ a tolerance strategy to maintain good health in the face of ongoing infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles,Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and nonimmune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other nongenetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein–protein interaction network for the mouse model rodent,Mus musculus, which we validate using our own expression network forM. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2‐related genes, Tyrosine‐protein kinase BTK and Tyrosine‐protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease.