(A) Control and Ptf1a cKO mice were administered TM (0.25 mg/g) on three consecutive days and sacrificed following a 2-week chase period. (B) Pancreas mass, measured as a percent of body weight, was significantly decreased in Ptf1a cKO mice 2 weeks after TM administration. (C, D) Immunofluorescence for the acinar enzyme carboxypeptidase A1 (CPA1) (red) and Cre reporter R26REYFP (green). Nuclei are labeled with DAPI (blue). Inset highlights EYFP+, CPA1-negative acinar cells forming duct-like structures in Ptf1a null pancreata. (E) Quantification of CPA1 expression by EYFP+ (Cre-recombined) cells in control and Ptf1a cKO pancreata (control n = 3, Ptf1a cKO n = 4, p < 0.01). (F, G) H&E staining of control and Ptf1a cKO pancreata 2 weeks after high-dose TM administration. (H, I) IHC for the duct marker CK19 highlighting areas of ADM in Ptf1a cKO pancreata. (J, K) Immunofluorescence for PTF1A (red) and the Cre reporter R26REYFP (green). White arrow indicates an EYFP+ cell expressing PTF1A in control; white arrowheads indicate non-recombined PTF1A+ cells; yellow arrowhead indicates a recombined, PTF1A-negative cell undergoing metaplasia in Ptf1a cKO. (L, M) Immunofluorescence for the duct transcription factor SOX9 (red) and the Cre reporter R26REYFP (green). Insets highlight restricted expression of SOX9 in controls and upregulation of SOX9 within EYFP+ acinar cells of Ptf1a cKO. Scale bars: (C, D) 100 µm, (F–I) 200 µm, (J, K) 50 µm, (L, M) 100 µm.