Diabetes and Tumor Formation in Transgenic Mice Expressing Reg I

• DOI: 10.1006/bbrc.2000.3813
• Publication Date: 2002-09-16T14:49:19Z
• Authors: Takashi Yamaoka; Kenji Yoshino; Taketo Yamada; Chiyoko Idehara; Mohammad O. Hoque; Maki Moritani; Katsuhiko Yoshimoto; Jun-ich Hata; Mitsuo Itakura
• Keywords: 0301 basic medicine; Mice, Transgenic; Neoplasms, Experimental; Diabetes Mellitus, Experimental; Mice, Inbred C57BL; Islets of Langerhans; Mice; 03 medical and health sciences; Phenotype; Mice, Inbred DBA; Animals; Insulin; Regeneration; Female; RNA, Messenger; Transgenes

To examine the effect of overexpressed regenerating gene (Reg) I on pancreatic beta-cells, we generated transgenic mice expressing Reg I in islets (Reg-Tg mice). Three lines of Reg-Tg mice were established. In line-1 Reg-Tg mice, the expression level of Reg 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 by apoptosis of beta-cells, as well as various malignant tumors. In addition to the decrease in beta-cells, compensatory islet regeneration and proliferation of ductal epithelial cells were observed in line-1 Reg-Tg mice. Because Reg I protein was secreted primarily into pancreatic ducts from acinar cells, it may primarily stimulate the proliferation of ductal epithelial cells, and not beta-cells, and their differentiation into islets. Moreover, the tumor-promoting activity of Reg I protein should be considered for its possible clinical applications.