Figure 8.

Ductal deletion of Hnf1b promotes PanIN progression in a Kras-activated context. Sox9-Cre^ER;Hnf1b^fl/fl mutants were crossed with Elas-tTA; TetO-Flpase; Kras^G12V mice (referred to as Kras) to obtain Sox9-Cre^ER;Hnf1b^fl/fl;Elas-tTA; TetO-Flpase; Kras^G12V (referred to as mutant;Kras) that combined perinatal inactivation of Hnf1b in ducts and oncogenic activation of Kras^G12V in acinar cells. Analyses of the pancreata were performed at 5 months. (A) H&E staining. (B) Alcian blue staining. (C) Claudin 18 (brown) immunostaining. (D) Quantification of the surface of the lesions stained with Alcian blue. (E) Quantification of the number of lesions per cm². (F) Quantification of the size of the lesions. (G–K) High-grade PanINs in mutant;Kras by (G–J) H&E staining and (K) Alcian Blue staining. Some lesions present marked cytologic and architectural atypia with the formation of branching papillae. Nuclei are enlarged and hyperchromatic with focal nuclear stratification. Scale bars: 100 μm. Mutants, n = 5; Kras, n = 4; mutant;Kras, n = 3. *P < .05; ***P < .001.