(a) Schematic of MADM-mediated LOH of p53. Efficient Cre-mediated intra-chromosomal recombination deletes the transcriptional/translational STOP cassette inducing oncogenic Kras activation. Less efficient Cre-mediated inter-chromosomal recombination following DNA replication (during G2 phase) leads to reconstitution of GFP and tdTomato on separate chromosomes before cell division. This diagram was adapted with permission from the original MADM schematic21. (b) X segregation of chromosomes following mitotic recombination (G2-X) results in genetically distinct daughter cells: p53KO/KO (green, GFP+/tdTomato−) and p53WT/WT (red, GFP−/tdTomato+) cells. Z-segregation (G2-Z) leads to the generation of yellow (GFP+/tdTomato+) and colourless (GFP−/TdTomato−) p53KO/WT cells. (c) Cre-mediated inter-chromosomal recombination during G0 or G1 phase results in the production of yellow p53KO/WT from colourless p53KO/WT cells. The MADM system affords faithful correlation between the expression of a specific genetically encoded fluorescence marker and genotype.