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bioRxiv · 10.1101/2024.05.17.592915

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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Abstract

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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Farre Diaz, C., Kabrani, E., Winkler, W., Salomon, C., Wunderlich, F. T., Janz, M., Rajewsky, K.. 2024-05-17. In vivo sequential mutagenesis in germinal center B cells using a dual-recombinase approach: FOXO1 re-expression upon FOXO1 knockout rescues class switch recombination. https://doi.org/10.1101/2024.05.17.592915

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