GENETIC-VARIATION AMONG 129 SUBSTRAINS AND ITS IMPORTANCE FOR TARGETED MUTAGENESIS IN MICE

Targeted mutagenesis in mice, a powerful tool for the analysis of gene function and human disease, makes extensive use of 129 mouse substrai ns. Although all are named 129, we document that outcrossing of these substrains, both deliberate and accidental, has lead to extensive gene tic 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, includin g: homologous recombination frequencies, preparation of inbred animals , and availability of appropriate controls. Based on these considerati ons we suggest a number of recommendations for future experimental des ign.