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The usefulness of genetically modified mice is discussed critically. Nevertheless, their number has increased dramatically over the past years. A principle for the use these mice is the isolation of DNA to determine whether an individual carries the genetic modification or not. This "genotyping" is usually done by invasive tissue sampling, e.g. tail biopsies, which likely causes discomfort and pain to the animals and is therefore discussed in animal welfare regulations. Although non-invasive tissue sampling by stool samples was already described over 10 years ago, it is not commonly used so far. In the present study we therefore tested the practicality of this method by the use of three commercial kits for genotyping and compared the results to those attained using tail biopsies. Our data shows that DNA isolation from stool samples is practical, sensitive and effective. In addition, the possibility of repeated sampling represents a clear advantage to invasive genotyping. Therefore, this method represents a useful tool in the 3R concept, since replacement of invasive tissue sampling refines the use of transgenic mice.