Cell子刊：常用的C57Bl/6小鼠存在免疫缺陷或影响研究结果

2016年5月22日--在一项新的研究中，来自美国麻省总医院拉根研究所（Ragon Institute）和加州大学圣地亚哥分校的研究人员在常用的C57Bl/6小鼠品系中发现一种被称作基因重复的突变，这可能影响以这些动物为实验对象的研究结果。这种突变破坏Dock2基因的功能，导致免疫缺陷。相关研究结果于2016年5月19日在线发表在Cell Reports期刊上，论文标题为“Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain”。

研究人员在这篇论文中写道，“鉴于这些发现，已发表的将C57BL/6小鼠为作为对照、实验动物或者用于回交实验的涉及免疫或造血表型的研究将需要重新解读。”

来自拉根研究所的Vinay Mahajan和同事们之前已观察到经过基因改造具有缺陷性Siae基因的小鼠存在多种免疫系统缺陷，包括边缘带B细胞数量下降和CD8+记忆T细胞数量增加。他们将这些小鼠与从实验室动物供应商Harlan Sprague Dawley购买的C57Bl/6小鼠回交数代，结果发现所产生的小鼠后代仍然具有同样的免疫表型。

通过对这些小鼠品系进行全基因组测序和研究它们的单核苷酸多态性（SNPs），研究人员鉴定出第11号染色体上的Dock2基因发生重复，正是这种基因重复导致观察到的免疫功能改变。

在2009年的一项研究（Journal of Experimental Medicine, 16 January 2009, 206:125-138, doi:10.1084/jem.20081399）中，研究人员发现另外两种基因敲除小鼠品系携带着意料之外的突变，这些突变导致B细胞发育存在缺陷。

Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain

doi:10.1016/j.celrep.2016.04.080

Vinay S. Mahajan3, Ezana Demissie3, Hamid Mattoo, Vinay Viswanadham, Ajit Varki, Robert Morris, Shiv Pillai

We describe a homozygous copy-number variant that disrupts the function of Dock2 in a commercially available C57BL/6 mouse strain that is widely used for backcrossing. This Dock2 allele was presumed to have spontaneously arisen in a colony of Irf5 knockout mice. We discovered that this allele has actually been inadvertently backcrossed into multiple mutant mouse lines, including two engineered to be deficient in Siae and Cmah. This particular commercially obtained subline of C57BL/6 mice also exhibits several striking immune phenotypes that have been previously described in the context of Dock2 deficiency. Inadvertent backcrossing of a number of gene-targeted mice into this background has complicated the interpretation of several immunological studies. In light of these findings, published studies involving immune or hematopoietic phenotypes in which these C57BL/6 mice have been used as controls, as experimental animals, or for backcrossing will need to be reinterpreted.