A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains
Open accessAbstract
Background: 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. Results: 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. Conclusions: 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.
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The species, strain, substrain, sex, weight, and age of animals are critical factors that can influence most experimental results.
“The species, strain, substrain, sex, weight, and age of animals are critical factors that can influence most experimental results [103–107].”
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The Discussion reports phenotypic differences between C57BL/6J and C57BL/6N mice that may affect comparisons of experimental results, and the Results describe some differences by sex. The paper does not establish that species, weight, or age influence results, or that the listed factors influence most experimental results. The indexed passages have no page numbers. (LLM, conf=0.87)
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“While one goal of sustaining a single inbred line is to limit interlaboratory artifacts, research on B6 mice reveals that genetic drift and mixed background breeding have introduced a number of variants since the first draft of the mouse reference genome (Sarsani et al., 2019; Simon et al., 2013).”
- Authors
- Simon, M. M., Greenaway, S., White, J. K., Fuchs, H., Gailus-Durner, V., Wells, S., Sorg, T., Wong, K., Bedu, E., Cartwright, E. J., Dacquin, R., Djebali, S., Estabel, J., Graw, J., Ingham, N. J., Jackson, I. J., Lengeling, A., Mandillo, S., Marvel, J., Meziane, H., Preitner, F., Puk, O., Roux, M., Adams, D. J., Atkins, S., Ayadi, A., Becker, L., Blake, A., Brooker, D., Cater, H., Champy, M.-F., Combe, R., Danecek, P., di Fenza, A., Gates, H., Gerdin, A.-K., Golini, E., Hancock, J. M., Hans, W., Hölter, S. M., Hough, T., Jurdic, P., Keane, T. M., Morgan, H., Müller, W., Neff, F., Nicholson, G., Pasche, B., Roberson, L.-A., Rozman, J., Sanderson, M., Santos, L., Selloum, M., Shannon, C., Southwell, A., Tocchini-Valentini, G. P., Vancollie, V. E., Westerberg, H., Wurst, W., Zi, M., Yalcin, B., Ramirez-Solis, R., Steel, K. P., Mallon, A.-M., de Angelis, M. H., Herault, Y., & Brown, S. D.
- Affiliations
- Mary Lyon Centre at MRC Harwell (GB)
- Wellcome Sanger Institute (GB)
- Helmholtz Munich (DE)
- Centre National de la Recherche Scientifique (FR)
- University of Manchester (GB)
- Structure Fédérative de Recherche Biosciences (FR)
- Western General Hospital (GB)
- Roslin Institute (GB)
- National Research Council (IT)
- Helmholtz Centre for Infection Research (DE)
- Centre Hospitalier Universitaire Vaudois (CH)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Brown, Steve DM
- ORCID
- Simon, Michelle M
- White, Jacqueline K
- Fuchs, Helmut
- Wells, Sara
- Sorg, Tania
- Wong, Kim
- Cartwright, Elizabeth J
- Djebali, Sophia
- Graw, Jochen
- Ingham, Neil J
- Jackson, Ian J
- Lengeling, Andreas
- Mandillo, Silvia
- Marvel, Jacqueline
- Puk, Oliver
- Roux, Michel
- Adams, David J
- Ayadi, Abdel
- Becker, Lore
- Blake, Andrew
- Cater, Heather
- Combe, Roy
- Danecek, Petr
- Gates, Hilary
- Golini, Elisabetta
- Hancock, John M
- Hans, Wolfgang
- Hölter, Sabine M
- Keane, Thomas M
- Müller, Werner
- Nicholson, George
- Rozman, Jan
- Selloum, Mohammed
- Vancollie, Valerie E
- Westerberg, Henrik
- Wurst, Wolfgang
- Zi, Min
- Yalcin, Binnaz
- Steel, Karen P
- Mallon, Ann-Marie
- Brown, Steve DM
- Venue
- Genome Biology
- Published
- 2013-07-31
- Volume
- 14
- Issue
- 7
- Pages
- R82-R82
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC4053787
- OpenAlex
- W2109276098
- Cited by
- 507
- References
- 1
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- FWCI
- 19.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- IRIS (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- HZI (Helmholtz Centre for Infection Research) (submittedVersion)
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- Site cant be reached (submittedVersion)
- DZNE Pub (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (100669, grant number 098051, 098051)
- Cancer Research UK (13031)
- University of Oxford
- European Commission (LSHG-CT-2006-037188)
- Agence Nationale de la Recherche (ANR-10-INBS-07, ANR-10, ANR-10-INBS-0007)
- Consiglio Nazionale delle Ricerche
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Technische Universität München
- Université de Lausanne
- PHENOMIN (ANR-10-INBS-07)
- Medical Research Council (MC_qA137918)
- Biotechnology and Biological Sciences Research Council (BBS/E/D/20231759)
- CHIST-ERA
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- C57BL/6J mice, C57BL/6N, inbred mouse strains, strain comparison, single nucleotide polymorphisms, indels, structural variants, coding variants, phenotypic differences, knockout mouse models, penetrance and expressivity, candidate genes
- MeSH terms
- Animals, Behavior, Animal, Eye, Female, Femur, Hypersensitivity, Killer Cells, Natural, Listeriosis, Male, Mice, Inbred C57BL, Phenotype, Spleen, Genome, Maze Learning, Polymorphism, Single Nucleotide, INDEL Mutation, X-Ray Microtomography, Disease Resistance
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