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Defining Genetic Variation in Widely Used Congenic and Backcrossed Mouse Models Reveals Varied Regulation of Genes Important for Immune Responses.
Immunity ( IF 25.5 ) Pub Date : 2019-06-24 , DOI: 10.1016/j.immuni.2019.05.006 Danielle A Chisolm 1 , Wayne Cheng 1 , Shelby A Colburn 1 , Aaron Silva-Sanchez 2 , Selene Meza-Perez 2 , Troy D Randall 2 , Amy S Weinmann 1
Immunity ( IF 25.5 ) Pub Date : 2019-06-24 , DOI: 10.1016/j.immuni.2019.05.006 Danielle A Chisolm 1 , Wayne Cheng 1 , Shelby A Colburn 1 , Aaron Silva-Sanchez 2 , Selene Meza-Perez 2 , Troy D Randall 2 , Amy S Weinmann 1
Affiliation
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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.
中文翻译：
在广泛使用的同基因和回交小鼠模型中定义遗传变异揭示了对免疫反应重要的基因的各种调节。
遗传变异影响个体和用于模拟免疫反应的小鼠品系中基因组的解释方式。我们开发了利用下一代测序数据集来鉴定同基因和回交小鼠模型中基因和增强子元件序列变异的方法。我们在广泛使用的B6-CD45.2和B6.SJL-CD45.1同基因模型中定义了遗传变异，并根据供应商的来源确定了保留在B6.SJL-CD45.1菌株中的SJL遗传含量的实质差异。老鼠。在至少一个B6.SJL-CD45.1小鼠供应商来源中，编码PD-1，CD62L，Bcl-2，组织蛋白酶E和Cxcr4的基因在SJL遗传含量之内。SJL遗传含量影响CD4 + T辅助1细胞中的增强子，基因调控，蛋白质表达和氨基酸含量，而且感染流感的小鼠在B6.SJL-CD45.1 T卵泡辅助细胞上的Cxcr4表达降低。这些发现提供了有关实验变量的信息，并有助于创建解释遗传变量的方法。
更新日期：2019-06-24
中文翻译：
在广泛使用的同基因和回交小鼠模型中定义遗传变异揭示了对免疫反应重要的基因的各种调节。
遗传变异影响个体和用于模拟免疫反应的小鼠品系中基因组的解释方式。我们开发了利用下一代测序数据集来鉴定同基因和回交小鼠模型中基因和增强子元件序列变异的方法。我们在广泛使用的B6-CD45.2和B6.SJL-CD45.1同基因模型中定义了遗传变异，并根据供应商的来源确定了保留在B6.SJL-CD45.1菌株中的SJL遗传含量的实质差异。老鼠。在至少一个B6.SJL-CD45.1小鼠供应商来源中，编码PD-1，CD62L，Bcl-2，组织蛋白酶E和Cxcr4的基因在SJL遗传含量之内。SJL遗传含量影响CD4 + T辅助1细胞中的增强子，基因调控，蛋白质表达和氨基酸含量，而且感染流感的小鼠在B6.SJL-CD45.1 T卵泡辅助细胞上的Cxcr4表达降低。这些发现提供了有关实验变量的信息，并有助于创建解释遗传变量的方法。
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