Role of the amino-terminal domain of simian virus 40 early region in inducing tumors in secretin-expressing cells in transgenic mice Christelle Ratineau,

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Role of the amino-terminal domain of simian virus 40 early region in inducing tumors in secretin-expressing cells in transgenic mice Christelle Ratineau, Anne Ronco, Andrew B. Leiter Gastroenterology Volume 119, Issue 5, Pages 1305-1311 (November 2000) DOI: 10.1053/gast.2000.19278 Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 1 Construction of transgenes. (A) Diagram of a transgene used previously, containing the entire early region of SV40 under control of 1.6-kb 5'-flanking sequence of the rat secretin gene, encoding both small t and large T antigens. (B) Diagrams illustrating SV40 early-region mutants used in the present study. Δt contains a deletion within the large T intron that abolishes the production of small t. The mutant Δt dl1135, in addition, contains the dl1135 deletion that results in the expression of Tag lacking amino acids 17–27. Gastroenterology 2000 119, 1305-1311DOI: (10.1053/gast.2000.19278) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 2 Islet cell tumorigenesis in Tag Δt transgenic mice. (A) H&E staining from a large, well-vascularized tumor in a 3-month-old mouse. (B–F) Nuclear immunostaining for Tag on pancreas sections of e17.5 (B), P1 (newborn; C), P30 (1-month-old; D), and adult (3-month-old; E). Tag Δt transgenic mouse. (Bar = 50 μm for A and E; 25 μm for B–D.) Gastroenterology 2000 119, 1305-1311DOI: (10.1053/gast.2000.19278) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 3 Characterization of islet cell tumors as insulinomas. Immunostaining for (A) insulin, (B) glucagon, (C) somatostatin, and (D) peptide YY in a pancreatic tumor of a 3-month-old Tag Δt mouse. Normal-appearing islets in a Tag Δt dl1135 transgenic mouse stained for (E) insulin, (F) glucagon, (G) somatostatin, and (H) peptide YY. (Bar = 50 μm for A and E; 25 μm for D and F–H; 12.5 μm for B–C.) Gastroenterology 2000 119, 1305-1311DOI: (10.1053/gast.2000.19278) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 4 Large T antigen expression in the small intestine of transgenic mice expressing (A) the Tag Δt mutant, (B) Tag Δt dl1135, or (C) the entire SV40 early region. Immunostaining for Tag in single epithelial cells in the small intestine of a 3-month-old Tag Δt mouse (A) or a 3-month-old Tag Δt dl1135 mouse (B). Large T antigen immunostaining of a small intramucosal tumor showing distorted structure of a single villus in a 6-week-old secretin SV40 early-region transgenic mouse (C). (Bar = 100 μm for C; 25 μm for A and B.) Gastroenterology 2000 119, 1305-1311DOI: (10.1053/gast.2000.19278) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 5 Large T antigen expression in lymphomas of Tag Δt transgenic animals. Strong nuclear Tag staining in lymphomas developed in the (A) spleen and (B) thymus of a 3-month-old Tag Δt mouse (bar = 50 μm). Gastroenterology 2000 119, 1305-1311DOI: (10.1053/gast.2000.19278) Copyright © 2000 American Gastroenterological Association Terms and Conditions