Diabetes and tumor formation in transgenic mice expressing Reg I

To examine the effect of overexpressed regenerating gene (Reg) I on pancrea tic beta -cells, we generated transgenic mice expressing Beg I in islets (R eg-Tg mice). Three lines of Reg-Tg mice were established. In line-1 Reg-Tg mice, the expression level of Beg I mRNA in islets was 7 times higher than those in lines 2 and 3 of Reg-Tg mice, and line 1 mice developed diabetes b y apoptosis of beta -cells, as well as various malignant tumors. In additio n to the decrease in beta -cells, compensatory islet regeneration and proli feration of ductal epithelial cells were observed in line-1 Reg-Tg mice. Be cause Beg I protein was secreted primarily into pancreatic ducts from acina r cells, it may primarily stimulate the proliferation of ductal epithelial cells, and not p-cells, and their differentiation into islets. Moreover, th e tumor-promoting activity of Beg I protein should be considered for its po ssible clinical applications. (C) 2000 Academic Press.