FOXO1 re-expression with a dual-recombinase allele rescues class switching in germinal center B cells
Modeling complex (patho)physiological processes by sequential targeted mutagenesis in mice is limited by the lack of precision of cellular targeting 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 in GCBCs in vivo, followed by time-controlled, efficient Dre-mediated FOXO1 re-expression in the same cells, leading to functional rescue of GC compartmentalization and class switch recombination. The present approach can be easily adapted to other cellular contexts.
Authors
- Wiebke Winkler (ORCID: https://orcid.org/0000-0001-8807-9259)
- Klaus Rajewsky (ORCID: https://orcid.org/0000-0002-6633-6370)
- Eleni Kabrani (ORCID: https://orcid.org/0000-0003-0834-9912)
- E. Blanc
- D. Beule
- Martin Janz (ORCID: https://orcid.org/0000-0002-1127-0044)
- Claudia Salomon
- Brigitte Wollert-Wulf
- Carlota Farré Díaz
- F. Thomas Wunderlich
Institutions
- Helmholtz Association of German Research Centres (DE)
- Max Delbrück Center (DE)
- Humboldt-Universität zu Berlin (DE)
- Max Planck Institute for Metabolism Research (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- University Hospital Cologne (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1084/jem.20241136
- Primary Topic
- FOXO transcription factor regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Krebshilfe