title: Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain.
abstract: 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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Vinay S
authors.initials: VS
authors.lastname: Mahajan
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Ezana
authors.initials: E
authors.lastname: Demissie
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mattoo
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Vinay
authors.initials: V
authors.lastname: Viswanadham
authors.affiliation: Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Morris
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA. Electronic address: pillai@helix.mgh.harvard.edu.
authors.forename: Shiv
authors.initials: S
authors.lastname: Pillai
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D020090:Chromosome Segregation; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D056915:DNA Copy Number Variations / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D020440:Gene Duplication; D018390:Gene Targeting; D056426:Genetic Loci; D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors; D007156:Immunologic Memory; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C471356:DOCK2 protein, mouse; D020690:GTPase-Activating Proteins; D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors