In vivo sequential mutagenesis in germinal center B cells using a dual-recombinase approach: FOXO1 re-expression upon FOXO1 knockout rescues class switch recombination
Farre Diaz, C.; Kabrani, E.; Winkler, W.; Salomon, C.; Wunderlich, F. T.; Janz, M.; Rajewsky, K.
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Modeling complex (patho)physiological processes by sequential mutagenesis in mice is limited by the lack of optimized genetic tools and complex breeding strategies. We present a new Cre/DreERT2 dual-recombinase germinal center B-cell (GCBC)- specific strain, with co-expression of the recombinases from a single allele. This enables highly efficient Cre-mediated FOXO1 knockout followed by time-controlled, efficient Dre-mediated FOXO1 re-expression and functional rescue in GCBCs, demonstrating suitability for precise targeted sequential mutagenesis in vivo.
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