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

• Main Authors: Mahajan, Vinay S (Author), Demissie, Ezana (Contributor), Mattoo, Hamid (Contributor), Viswanadham, Vinay (Contributor), Varki, Ajit (Author), Morris, Robert (Contributor), Pillai, Shiv (Contributor), Mahajan, Vinay S. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Ragon Institute of MGH, MIT and Harvard (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2016-07-18T17:02:35Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (NIH grant AI064930)
National Institutes of Health (U.S.) (NIH grant GM032373)