Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice

Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice
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DOI:
10.1038/ng0597-19
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发表时间:
1997-05-01
期刊:
影响因子:
30.8
通讯作者:
Sharp, JJ
Sharp, JJ
中科院分区:
生物学1区
文献类型:
--
作者:
Simpson, EM;Linder, CC;Sharp, JJ

文献摘要

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小鼠的靶向突变是分析基因功能和人类疾病的有力工具,它广泛使用了129个小鼠亚系。虽然都被命名为129,但我们的文件表明,这些亚株的异交,无论是故意的还是偶然的,都导致了亚株及其衍生的胚胎干细胞之间广泛的遗传变异。更清楚地了解129亚株的可变性,可以考虑其对靶向技术的负面影响,包括:同源重组频率、近亲交配动物的准备以及适当对照的可用性。基于这些考虑,我们对未来的实验设计提出了一些建议。
Targeted mutagenesis in mice, a powerful tool for the analysis of gene function and human disease, makes extensive use of 129 mouse substrains. Although all are named 129, we document that outcrossing of these substrains, both deliberate and accidental, has lead to extensive genetic variability among substrains and embryonic stem cells derived from them. This clearer understanding of 129 substrain variability allows consideration of its negative impact on targeting technology, including: homologous recombination frequencies, preparation of inbred animals, and availability of appropriate controls. Based on these considerations we suggest a number of recommendations for future experimental design.