Mouse models to investigate in situ cell fate decisions induced by TP53 and other factors

Imaging data set from p21-IRES-GFP and Puma-tdTomato mice associated with the manuscript EMBOJ-2023-114787

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their fate to be followed over time. For example, the tumour suppressor TP53/TRP53 can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types. To be able to examine this, we developed triple-FLAG TRP53 knock-in mice for TRP53 pull-down and two TRP53 response reporter mice, knocking tdTomato or GFP into the Puma/Bbc3 or p21 gene loci, respectively. By crossing the reporter mice onto a TRP53-deficient background, we could show that these reporters reliably inform on TRP53-dependent and TRP53-independent initiation of the apoptotic as well as the cell cycle arrest/senescence programs in vitro and even in vivo.