Not All C57BL/6 Substrains Are Created Equal

我们最近报道，生物医学研究人员应该意识到C57BL/6亚株的遗传和表型差异。当在C57BL/6背景下用基因工程小鼠(GEM)进行研究时，这一知识尤其重要。将GEM与错误的C57BL/6亚株对照错误配对可能会导致错误和误导性的结果，正如我们最近发现的那样，研究c-Jun N末端激酶2在对乙酰氨基酚和刀豆蛋白A诱导的肝损伤中的病理作用。 最近用外显子阵列和RNA-SEQ技术对杰克逊实验室的醋氨酚处理的C57BL/6J小鼠和Taconic Farm的C57BL/6NTac小鼠的肝脏匀浆进行了无偏倚的全基因组表达分析，发现这两个亚系C57BL/6小鼠在表达基因、剪接变体和信号核苷酸变异方面存在许多差异。其中许多遗传事件在蛋白质水平上得到了证实。 结论：预计对我们的基因表达数据的进一步研究和分析将发现危险因素，这些因素可能在确定患者对药物引起的肝损伤的易感性方面发挥作用。

We recently reported that biomedical researchers should be aware of genetic and phenotypic differences in C57BL/6 substrains. This knowledge is particularly important when doing studies with genetically engineered mice (GEM) on a C57BL/6 background. Mispairing of GEM with the wrong C57BL/6 substrain control can lead to erroneous and misleading findings as we found recently studying the pathological role of c-Jun N-terminal kinase 2 in acetaminophen- and concanavalin A -induced liver injury. Recent unbiased genome-wide expression analyses with exon array and RNA-SEQ technologies of liver homogenates from acetaminophen-treated C57BL/6J mice from the Jackson Laboratory and C57BL/6NTac mice from Taconic Farms revealed numerous differences in expressed genes, spliced variants, and signal nucleotide variations between the two substrains of C57BL/6 mice. Many of these genetic events were confirmed at the protein level. Conclusion: It is anticipated that further studies and analyses of our genetic expression data will uncover risk factors that may play roles in determining susceptibility of patients to drug-induced liver injury.