2016年5月22日/生物谷BIOON/--在一項新的研究中，來自美國麻省總醫院拉根研究所（Ragon Institute）和加州大學聖地牙哥分校的研究人員在常用的C57Bl/6小鼠品系中發現一種被稱作基因重複的突變，這可能影響以這些動物為實驗對象的研究結果。這種突變破壞Dock2基因的功能，導致免疫缺陷。相關研究結果於2016年5月19日在線發表在Cell Reports期刊上，論文標題為「Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain」。
研究人員在這篇論文中寫道，「鑑於這些發現，已發表的將C57BL/6小鼠為作為對照、實驗動物或者用於回交實驗的涉及免疫或造血表型的研究將需要重新解讀。」
來自拉根研究所的Vinay Mahajan和同事們之前已觀察到經過基因改造具有缺陷性Siae基因的小鼠存在多種免疫系統缺陷，包括邊緣帶B細胞數量下降和CD8+記憶T細胞數量增加。他們將這些小鼠與從實驗室動物供應商Harlan Sprague Dawley購買的C57Bl/6小鼠回交數代，結果發現所產生的小鼠後代仍然具有同樣的免疫表型。
通過對這些小鼠品系進行全基因組測序和研究它們的單核苷酸多態性（SNPs），研究人員鑑定出第11號染色體上的Dock2基因發生重複，正是這種基因重複導致觀察到的免疫功能改變。
在2009年的一項研究（Journal of Experimental Medicine, 16 January 2009, 206:125-138, doi:10.1084/jem.20081399）中，研究人員發現另外兩種基因敲除小鼠品系攜帶著意料之外的突變，這些突變導致B細胞發育存在缺陷。（生物谷 Bioon.com）
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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.