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. 2020 Jun 4;11:2817. doi: 10.1038/s41467-020-16309-2

Fig. 1. AGO2 is essential for progression of precursor PanIN lesions to PDAC.

Fig. 1

a Schematic of the conditionally activated endogenous alleles of KRASG12D and AGO2 used in the study to generate the AGO2fl/fl;KRASG12D;p48Cre experimental mice. b Representative images of H&E and AGO2 IHC analysis of pancreata obtained from AGO2+/+;p48Cre and AGO2fl/fl;p48Cre genotypes. Orange and black arrows indicate AGO2 expression in acinar cells and islets of Langerhans, respectively. Scale bar, 100 µm. c Representative H&E and IHC analysis for AGO2 in pancreata obtained from 12-week old mice from the AGO2+/+;KRASG12D;p48Cre and AGO2fl/fl;KRASG12D;p48Cre genotypes. Orange and black arrows indicate AGO2 staining in the PanIN and stromal regions, respectively. Scale bar, 100 µm. d Scatter plot showing the weight of pancreata obtained from 10 AGO2+/+;KRASG12D;p48Cre, 17 AGO2fl/+;KRASG12D;p48Cre, and 14 AGO2fl/fl;KRASG12D;p48Cre mice aged over 400 days. Two sided t-test was performed to determine the P value and error bars are mean values +/− SEM. e Histogram showing average number of early and late PanIN lesions observed in 11 mice each of AGO2+/+;KRASG12D;p48Cre, AGO2fl/+;KRASG12D;p48Cre, and AGO2fl/fl;KRASG12D;p48Cre genotypes at 400 days. The number of early/ late PanINs and PDAC within pancreatic sections from each animal were counted as a percentage. For AGO2fl/fl;KRASG12D;p48Cre mice, only lesions that do not express AGO2 have been included. f Kaplan–Meier curve for tumor-free survival of AGO2+/+;KRASG12D;p48Cre, AGO2fl/+;KRASG12D;p48Cre, and AGO2fl/fl; KRASG12D;p48Cre mice aged over 500 days. g Chart showing PDAC (within the pancreas), the different metastatic lesions, and abnormal pathologies (black boxes) observed in each mouse of the indicated genotypes aged over 500 days. Gray boxes in the AGO2fl/fl;KRASG12D;p48Cre group indicate abnormal pathology observed at the indicated site and are addressed in further detail in Supplementary Fig. 4. The number of mice indicated in this figure represent biologically independent individuals.