Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Immunity. 2019 Jul 16;51(1):155-168.e5. doi: 10.1016/j.immuni.2019.05.006. Epub 2019 Jun 24.
Genetic variation influences how the genome is interpreted in individuals and in mouse strains used to model immune responses. We developed approaches to utilize next-generation sequencing datasets to identify sequence variation in genes and enhancer elements in congenic and backcross mouse models. We defined genetic variation in the widely used B6-CD45.2 and B6.SJL-CD45.1 congenic model, identifying substantial differences in SJL genetic content retained in B6.SJL-CD45.1 strains on the basis of the vendor source of the mice. Genes encoding PD-1, CD62L, Bcl-2, cathepsin E, and Cxcr4 were within SJL genetic content in at least one vendor source of B6.SJL-CD45.1 mice. SJL genetic content affected enhancer elements, gene regulation, protein expression, and amino acid content in CD4 T helper 1 cells, and mice infected with influenza showed reduced expression of Cxcr4 on B6.SJL-CD45.1 T follicular helper cells. These findings provide information on experimental variables and aid in creating approaches that account for genetic variables.
遗传变异影响个体基因组的解读以及用于模拟免疫反应的小鼠品系。我们开发了利用下一代测序数据集的方法，以鉴定同基因和回交小鼠模型中基因和增强子元件的序列变异。我们定义了广泛使用的 B6-CD45.2 和 B6.SJL-CD45.1 同基因模型中的遗传变异，根据小鼠的供应商来源，确定了 B6.SJL-CD45.1 品系中保留的 SJL 遗传物质的大量差异。编码 PD-1、CD62L、Bcl-2、组织蛋白酶 E 和 Cxcr4 的基因至少在一个 B6.SJL-CD45.1 小鼠的供应商来源中存在于 SJL 遗传物质中。SJL 遗传物质影响 CD4 T 辅助 1 细胞中的增强子元件、基因调控、蛋白表达和氨基酸含量，感染流感的小鼠显示 B6.SJL-CD45.1 T 滤泡辅助细胞中 Cxcr4 的表达降低。这些发现提供了有关实验变量的信息，并有助于创建考虑遗传变量的方法。
