Hyperplasia and tumors of the islets of Langerhans in mice bearing an elastase I-SV40 T-antigen fusion gene.
Transgenic mice bearing a fusion gene consisting of rat elastase I 5' flanking DNA fused to the early-coding (T-antigen) region of the SV40 genome (ELSV mice) develop carcinomas of the acinar cells of the exocrine pancreas. Histopathological examination of pancreatic tissue from 79 such animals revealed that, in addition to acinar cell neoplasms, ELSV mice develop two distinct lesions of the islets of Langerhans. By the age of 26 weeks, 36% of the mice had developed insulinomas. Starting at 8 weeks of age, the mice also developed D (somatostatin)-cell hyperplasia, which began at the periphery of the islets but which in advanced cases resulted in nearly complete replacement of other islet cell types by D-cells. By 26 weeks of age, 85% of the mice examined demonstrated the D-cell abnormality. Both the insulinomas and D-cell lesions were negative by immunohistochemistry for T-antigen, which was, however, demonstrated in acinar cell neoplasms using a monoclonal antibody against a C-terminal T-antigen epitope. Insulinomas have been described in other SV40 transgenic mice, particularly when the SV40 enhancer is not included in the transgene, suggesting that the presence of native SV40 enhancer may ordinarily suppress the expression of T-antigen in pancreatic beta-cells. The somatostatin-cell lesion is unique to the ELSV model; it may be neoplastic or represent a response to the growth and neoplastic changes occurring simultaneously in the exocrine pancreas.
Bell
R H
RH
Department of Pathology, Dartmouth Medical School, Hanover, NH 03756.
Memoli
V A
VA
Longnecker
D S
DS
D007516:Adenoma, Islet Cell / Q000473:pathology*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D003001:Cloning, Molecular; D006965:Hyperplasia; D007340:Insulinoma / Q000209:etiology / Q000473:pathology*; D007515:Islets of Langerhans / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D010196:Pancreatic Elastase / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000473:pathology*; D011401:Promoter Regions, Genetic
D000952:Antigens, Polyomavirus Transforming; D010196:Pancreatic Elastase