(a) Pancreas from a 5-week-old Pdx1-Cre-MADM-p53 mouse contains p53KO/KO (green, GFP+/tdTomato−), p53WT/WT (red, GFP−/tdTomato+) and p53KO/WT (yellow, GFP+/tdTomato+) acinar cells with normal appearance. (b) Low-grade pancreatic intraepithelial neoplasm (PanIN) in an 8-week-old Pdx1-Cre-K-MADM-p53 mouse. (c) High-grade PanIN in a 6-week-old Pdx1-Cre-K-MADM-p53 mouse. (d) PDAC in an 11-week-old Pdx1-Cre-K-MADM-p53 mouse. (e) Liver metastasis in a 10-week-old Pdx1-Cre-K-MADM-p53 mouse harbouring primary PDAC tumours in the pancreas. (f) Lymph node metastasis in a 10-week-old Pdx1-Cre-K-MADM-p53 mouse harbouring primary PDAC tumours in the pancreas. (g) Kaplan–Meier survival analysis of Kras and p53 mutant mouse models of PDAC. Pdx1-Cre-K-MADM-p53 mice (n=47, median survival 79 days) harbour intermediate median survival between Pdx1-Cre; LSL-KrasG12D/KrasWT (KC) homozygous p53 mutant (KC; p53flox/flox (n=9, median survival 43 days) and KC; p53LSL-R172H/flox (n=37, median survival 44 days)) and heterozygous p53 mutant (KC; p53flox/WT (n=7, median survival 154 days) and KC; p53LSL-R172H/WT (n=13, median survival 154 days)) models. Pdx1-Cre-K-MADM mice (with wild-type p53, n=20) have prolonged survival similar to that observed with KC mice lacking p53 mutation12. Control Pdx1-Cre-MADM-p53 (lacking LSL-KrasG12D, n=21) and K-MADM-p53 (lacking Pdx1-Cre, n=16) mice do not initiate pancreatic tumorigenesis. Blue, DAPI-stained nuclei. Scale bars, 100 μm (all). (a,b) were reproduced with permission from MIT.