氨诱导的小鼠急性肺损伤的遗传决定因素。
Genetic determinants of ammonia-induced acute lung injury in mice.
机构信息
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Unit of Integrated Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
出版信息
Am J Physiol Lung Cell Mol Physiol. 2021 Jan 1;320(1):L41-L62. doi: 10.1152/ajplung.00276.2020. Epub 2020 Oct 14.
Abstract
In this study, a genetically diverse panel of 43 mouse strains was exposed to ammonia, and genome-wide association mapping was performed employing a single-nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was used to help resolve the genetic determinants of ammonia-induced acute lung injury. The encoded proteins were prioritized based on molecular function, nonsynonymous SNP within a functional domain or SNP within the promoter region that altered expression. This integrative functional approach revealed 14 candidate genes that included , , , and , which had significant SNP associations, and , , , , , , and , which had suggestive SNP associations. Of these genes, , , , , and are particularly noteworthy and had pathophysiological roles that could be associated with acute lung injury in several ways.
摘要
在这项研究中，对一个包含 43 个不同品系的基因多样化的小鼠群体进行了氨暴露实验，并利用单核苷酸多态性 (SNP) 图谱进行了全基因组关联作图。采用转录组分析来帮助解析氨诱导的急性肺损伤的遗传决定因素。根据分子功能、功能域内的非同义 SNP 或改变表达的启动子区域内的 SNP，对编码蛋白进行了优先级排序。这种综合功能方法揭示了 14 个候选基因，包括 、 、 、 和 ，它们具有显著的 SNP 关联，以及 、 、 、 、 、 和 ，它们具有提示性的 SNP 关联。在这些基因中， 、 、 、 、 和 特别值得注意，它们具有与多种方式的急性肺损伤相关的病理生理学作用。
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