Genetic polymorphisms among C57BL/6 mouse inbred strains
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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)-Tyr c−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.
KeywordsGenetic background Phenotype Genotype Behaviour Transgenic mice Knockout mice Embryonic stem cells SNP
This work was supported by funds from the Spanish Ministry of Science and Innovation (MICINN, BIO2009-1297) and from CIBERER (INTRA/09/756,1) to LM and Red de Trastornos Adictivos, RD06/0001/0011, Plan Nacional Sobre Drogas, PR61/08-16415, and Ministerio de Ciencia e Innovación, SAF2008-03763, to JALM. EZ is supported by a fellowship from MICINN (PFPU). The authors are most grateful to Thomas J. Fielder, Ulrich Märki, Johannes Wilbertz and Elizabeth Williams for their useful comments and suggestions and, especially, their generous contribution of DNA and/or tissue samples from several mouse strains used in this study.
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