title: Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium.
abstract: The International Knockout Mouse Consortium (IKMC) introduces its targeted constructs into C57BL/6N embryonic stem cells. However, breeding with a Cre-recombinase and/or Flp-recombinase mouse is required for the generation of a null allele with the IKMC cassette. Many recombinase strains are in the C57BL/6J background, resulting in knockout animals on a mixed strain background. This can lead to variability in metabolic data and the use of improper control groups. While C57BL/6N and C57BL/6J are derived from the same parental C57BL/6 strain, there are key genotypic and phenotypic differences between these substrains. Many researchers may not even be aware of these differences, as the shorthand C57BL/6 is often used to describe both substrains. We found that 58% of articles involving genetically modified mouse models did not completely address background strain. This review will describe these two substrains and highlight the importance of separate consideration in mouse model development. Our aim is to increase awareness of this issue in the diabetes research community and to provide practical strategies to enable researchers to avoid mixed strain animals when using IKMC knockout mice.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Fontaine
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Wisconsin-Madison, Madison, WI William S. Middleton Memorial Veterans Hospital, Madison, WI dbd@medicine.wisc.edu.
authors.forename: Dawn Belt
authors.identifier: http://orcid.org/0000-0002-0239-4715
authors.initials: DB
authors.lastname: Davis
mesh_terms: D000818:Animals; D004254:DNA Nucleotidyltransferases; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005838:Genotype; D019426:Integrases; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics* / Q000378:metabolism; D008815:Mice, Inbred Strains / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012107:Research Design
chemical_list: C045073:Cre recombinase; D004254:DNA Nucleotidyltransferases; C045119:FLP recombinase; D019426:Integrases