Novel insights into the genetic background of genetically modified mice
Unclear or misclassified genetic background of laboratory rodents or a lack of strain awareness causes a number of difficulties in performing or reproducing scientific experiments. Until now, genetic differentiation between strains and substrains of inbred mice has been a challenge. We have developed a screening method for analyzing inbred strains regarding their genetic background. It is based on 240 highly informative short tandem repeat (STR) markers covering the 19 autosomes as well as X and Y chromosomes. Combination of analysis results for presence of known C57BL/6 substrain-specific mutations together with autosomal STR markers and the Y-chromosomal STR-haplotype provides a comprehensive snapshot of the genetic background of mice. In this study, the genetic background of 72 mouse lines obtained from 18 scientific institutions in Germany and Austria was determined. By analyzing only 3 individuals per genetically modified line it was possible to detect mixed genetic backgrounds frequently. In several lines presence of a mispairing Y chromosome was detected. At least every second genetically modified line displayed a mixed genetic background which could lead to unexpected and non-reproducible results, irrespective of the investigated gene of interest.
KeywordsGenetic background determination Genetically modified mice C57BL/6 Substrain-specific mutations Y chromosome STR-genotyping
Tissue samples of reference inbred strains were kindly provided by Dr. Thomas Grunwald. We thank Dr. Olaf Gelsen for critical reading of the manuscript. This work was supported by the European Regional Development Fund (EFRE Project No. 100210585).
Compliance with ethical standards
Conflict of interest
P. Dobrowolski is in an employment relationship with GVG Genetic Monitoring. M. Fischer was charged by GVG Genetic Monitoring to perform STR-analysis.
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