A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains
1 Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell Science Campus, OX11 0RD, UK
2 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
3 Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Ingolstädter Landstraße 1, Neuherberg, D-85764, Germany
4 Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Developmental Genetics, Ingolstädter Landstraße 1, Neuherberg, D-85764, Germany
5 Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Pathology, Ingolstädter Landstraße 1, Neuherberg, D-85764, Germany
6 Institut Clinique de la Souris, ICS/MCI, PHENOMIN, GIE CERBM, IGBMC, CNRS, INSERM, 1 Rue Laurent Fries, 67404 Illkirch-Graffenstaden Cedex, France
7 Faculty of Medical and Human Sciences, University of Manchester, Oxford Road, Manchester, MN13 9PT, UK
8 Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, MN13 9PT, UK
9 AniRA ImmOs phenotyping facility- SFR Biosciences Lyon Gerland- UMS3444/US8, 21 avenue Tony Garnier F-69007 Lyon, France
10 Medical Research Council Human Genetics Unit, IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
11 Infection and Immunity Division, Roslin Institute, University of Edinburgh, Easter Bush Veterinary Campus, Midlothian, EH25 9RG, UK
12 Consiglio Nazionale delle Ricerche- Cell Biology and Neurobiology Institute, Via E.Ramarini 32, 00015 Monterotondo Scala, Italy
13 Department of Infection Genetics, Helmholtz Centre for Infection Research, Inhoffenstraße 7, Braunschweig, 38124, Germany
14 Mouse Metabolic Facility of the Cardiomet Center, University Hospital, and Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland
15 Center for Integrative Genomics, University of Lausanne, Lausanne, CH-1015, Switzerland
16 Chair for Developmental Genetics, Technische Universität München, Arcisstr. 21, Munich, 80333, Germany
17 Max Planck Institute of Psychiatry, Kraepelinstrasse 2, Munich, 80804, Germany
18 Deutsches Zentrum für Neurodegenerative Erkrankungen, Schillerstrasse 44, Munich, 80336, Germany
Genome Biology 2013, 14:R82 doi:10.1186/gb-2013-14-7-r82Published: 31 July 2013
The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms.
We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems.
Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.