Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line |
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| Authors: | Elizabeth D. Hughes Yun Yan Qu Suzanne J. Genik Robert H. Lyons Christopher D. Pacheco Andrew P. Lieberman Linda C. Samuelson Igor O. Nasonkin Sally A. Camper Margaret L. Van Keuren Thomas L. Saunders |
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| Affiliation: | (1) Transgenic Animal Model Core, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(2) DNA Sequencing Core, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(3) Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(4) Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(5) Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(6) Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(7) Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;(8) University of Michigan Medical School, 2560 MSRB II Box 0674, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA;(9) Department of Pathology, Division of Neuropathology, Johns Hopkins University, Baltimore, Maryland 21205, USA |
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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. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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