Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line
Genetic variation in C57BL/6 ES cell lines and genetic instability in the Bruce4 C57BL/6 ES cell line
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DOI：
10.1007/s00335-007-9054-0
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发表时间：
2007-08-01
期刊：
影响因子：
2.5
通讯作者：
Saunders, Thomas L.
中科院分区：
文献类型：
--
作者：
Hughes, Elizabeth D.;Qu, Yun Yan;Saunders, Thomas L.
胚胎干细胞来源的转基因小鼠品系是基因功能分析的有力工具。尽管C57BL/6小鼠品系的ES细胞具有明确的遗传背景，但并未被广泛用于建立小鼠模型。我们用275个SSLP标记评估了6个这样的ES细胞系的遗传变异。与C57BL/6相比，Bruce4在34个SSLP标记上存在差异，在3条染色体上具有显著的杂合性。BL/6#3和DALE1 ES细胞株仅有3个SSLP标记不同。C2和WB6d ES细胞系在6个SSLP标记上存在差异。用现有的C57BL/6 ES细胞与标准的129小鼠品系ES细胞相比较，制作小鼠模型的效率是很重要的。我们评估了来自最广泛使用的C57BL/6 ES细胞系Bruce4的110个基因靶向ES细胞克隆和710个靶向129个ES细胞克隆的遗传稳定性(细胞变得非整倍体的趋势)。Bruce4克隆更有可能是非整倍体，不适合ES细胞-小鼠嵌合体的生产。尽管Bruce4ES细胞倾向于非整倍体并导致效率低下，但对于需要进行行为研究的模型和其他受益于特定C57BL/6背景的小鼠模型来说，使用Bruce4 ES细胞可能是有价值的。
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.