Functional Pancreatic β-Cell Line From SV40 T-Antigen Transgenic Mouse

Abstract

Cell line lgSV195, derived from a pancreatic tumor that arose in an SV40 T-antigen transgenic mouse, retains certain morphological and physiological characteristics of pancreatic β-cells throughout in vitro and in vivo passage. Insulin secretion is stimulated by exposure of these cells to fetal bovine serum and a combination of 3-isobutyl-1-methylxanthine and glutamine but not by concentrations of glucose in the physiological range. Insulin processing appears to be intact. Neither class I nor class II major histocompatibility complex (MHC) antigens are routinely expressed at the cell surface; however, MHC class I– but not class II–encoded gene products are detected after treatment with recombinant interferon-γ (IFN-γ) alone or in combination with tumor necrosis factor. Cytolysis of lgSV195 cells by SV40 T-antigen-specific H-2b-restricted lymphocytes is similarly dependent on IFN-γ pretreatment. These results emphasize that SV40 T-antigen transgenic mice are likely sources of cell lines that retain their differentiated function in vitro. The lgSV195 cell line provides an accessible model in which to investigate the control of gene expression and function of pancreatic β-cells.