Mice from the inbred C57BL/6 strain have been commonly used for the generation and analysis of transgenic and knockout animal models. However, several C57BL/6 substrains exist, and these are genetically and phenotypically different. In addition, each of these substrains can be purchased from different animal providers and, in some cases, they have maintained their breeding stocks separated for a long time, allowing genetic differences to accumulate due to individual variability and genetic drift. With the aim of describing the differences in the genotype of several C57BL/6 substrains, we applied the Illumina® Mouse Medium Density Linkage Mapping panel, with 1,449 single nucleotide polymorphisms (SNPs), to individuals from ten C57BL/6-related strains: C57BL/6JArc, C57BL/6J from The Jackson Lab, C57BL/6J from Crl, C57BL6/JRccHsd, C57BL/6JOlaHsd, C57BL/6JBomTac, B6(Cg)-Tyrc−2j/J, C57BL/6NCrl, C57BL/6NHsd and C57BL/6NTac. Twelve SNPs were found informative to discriminate among the mouse strains considered. Mice derived from the original C57BL/6J: C57BL/6JArc, C57BL/6J from The Jackson Lab and C57BL/6J from Crl, were indistinguishable. Similarly, all C57BL/6N substrains displayed the same genotype, whereas the additional substrains showed intermediate cases with substrain-specific polymorphisms. These results will be instrumental for the correct genetic monitoring and appropriate mouse colony handling of different transgenic and knockout mice produced in distinct C57BL/6 inbred substrains.
Al-Hasani K, Vadolas J, Voullaire L, Williamson R, Ioannou PA (2004) Complementation of alpha-thalassaemia in alpha-globin knockout mice with a 191 kb transgene containing the human alpha-globin locus. Transgenic Res 13:235–243PubMedCrossRefGoogle Scholar
Bothe GW, Bolivar VJ, Vedder MJ, Geistfeld JG (2004) Genetic and behaviorial differences among five inbred mouse strains commonly used in the production of transgenic and knockout mice. Genes Brain Behav 3:149–157PubMedCrossRefGoogle Scholar
Bryant CD, Zhang NN, Sokoloff G, Fanselow MS, Ennes HS, Palmer AA, McRoberts JA (2008) Behavioral differences among C57BL/6 substrains: implications for transgenic and knockout studies. J Neurogenet 22:315–331PubMedCrossRefGoogle Scholar
Festing M (1996) Origins and characteristics of inbred strains of mice. In: Lyon M, Rastan S, Brown S (eds) Genetic variants and strains of the laboratory mouse, 3rd edn. Oxford University Press, Oxford, pp 1537–1576Google Scholar
Freeman HC, Hugill A, Dear NT, Ashcroft FM, Cox RD (2006) Deletion of nicotinamide nucleotide transhydrogenase: a new quantitative trait locus accounting for glucose intolerance in C57BL/6J mice. Diabetes 55:2153–2156PubMedCrossRefGoogle Scholar
Mekada K, Abe K, Murakami A, Nakamura S, Nakata H, Moriwaki K, Obata Y, Yoshiki A (2009) Genetic differences among C57BL/6 substrains. Exp Anim 58:141–149PubMedCrossRefGoogle Scholar
Mulligan MK, Ponomarev I, Boehm SL 2nd, Owen JA, Levin PS, Berman AE, Blednov YA, Crabbe JC, Williams RW, Miles MF, Bergeson SE (2008) Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains. Genes Brain Behav 7:677–689PubMedCrossRefGoogle Scholar