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Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line

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Abstract

Genetically modified mouse strains derived from embryonic stem (ES) cells are powerful tools for gene function analysis. ES cells from the C57BL/6 mouse strain are not widely used to generate mouse models despite the advantage of a defined genetic background. We assessed genetic variation in six such ES cell lines with 275 SSLP markers. Compared to C57BL/6, Bruce4 differed at 34 SSLP markers and had significant heterozygosity on three chromosomes. BL/6#3 and Dale1 ES cell lines differed at only 3 SSLP makers. The C2 and WB6d ES cell lines differed at 6 SSLP markers. It is important to compare the efficiency of producing mouse models with available C57BL/6 ES cells relative to standard 129 mouse strain ES cells. We assessed genetic stability (the tendency of cells to become aneuploid) in 110 gene-targeted ES cell clones from the most widely used C57BL/6 ES cell line, Bruce4, and 710 targeted 129 ES cell clones. Bruce4 clones were more likely to be aneuploid and unsuitable for ES cell-mouse chimera production. Despite their tendency to aneuploidy and consequent inefficiency, use of Bruce4 ES cells can be valuable for models requiring behavioral studies and other mouse models that benefit from a defined C57BL/6 background.

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Acknowledgments

The authors thank Keith Childs, Tina Jones, Eric Sweeney, and Corey Ziebell for assistance with chromosome counts. This work was supported by grants from the National Institutes of Health (NIH) University of Michigan Transgenic Core NIH grants (CA46592, AR20557, AG13283, DK034933), The University of Michigan Center for Organogenesis, the Michigan Economic Development Corporation, and the Michigan Technology Tri-Corridor (Michigan Animal Models Consortium Grant 085P1000815), and by NIH grants R01HD034283 and R37HD030428 (SAC).

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Authors and Affiliations

  1. Transgenic Animal Model Core, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Elizabeth D. Hughes, Yun Yan Qu, Linda C. Samuelson, Sally A. Camper, Margaret L. Van Keuren & Thomas L. Saunders

  2. DNA Sequencing Core, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Suzanne J. Genik & Robert H. Lyons

  3. Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Robert H. Lyons

  4. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Christopher D. Pacheco & Andrew P. Lieberman

  5. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Linda C. Samuelson

  6. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Igor O. Nasonkin & Sally A. Camper

  7. Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Sally A. Camper & Thomas L. Saunders

  8. University of Michigan Medical School, 2560 MSRB II Box 0674, 1150 West Medical Center Drive, Ann Arbor, MI, 48109, USA

    Thomas L. Saunders

  9. Department of Pathology, Division of Neuropathology, Johns Hopkins University, Baltimore, Maryland, 21205, USA

    Igor O. Nasonkin

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  1. Elizabeth D. Hughes
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  2. Yun Yan Qu
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  3. Suzanne J. Genik
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  8. Igor O. Nasonkin
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  9. Sally A. Camper
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  10. Margaret L. Van Keuren
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  11. Thomas L. Saunders
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Correspondence to Thomas L. Saunders.

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Hughes, E.D., Qu, Y.Y., Genik, S.J. et al. Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line. Mamm Genome 18, 549–558 (2007). https://doi.org/10.1007/s00335-007-9054-0

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