Diabetes and Tumor Formation in Transgenic Mice Expressing Reg I

• Published in: Biochemical and biophysical research communications 2000-11, Vol.278 (2), p.368-376
• Main Authors: Yamaoka, Takashi, Yoshino, Kenji, Yamada, Taketo, Idehara, Chiyoko, Hoque, Mohammad O., Moritani, Maki, Yoshimoto, Katsuhiko, Hata, Jun-ich, Itakura, Mitsuo
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Female; Insulin - metabolism; Islets of Langerhans - metabolism; Islets of Langerhans - physiopathology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; neoplasm; Neoplasms, Experimental - genetics; pancreatic islet; Phenotype; Reg I; Reg I protein; regeneration; Regeneration - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transgenes; transgenic mouse
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3813

To examine the effect of overexpressed regenerating gene (Reg) I on pancreatic β-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 β-cells, as well as various malignant tumors. In addition to the decrease in β-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 β-cells, and their differentiation into islets. Moreover, the tumor-promoting activity of Reg I protein should be considered for its possible clinical applications.