Diabetes and tumor formation in transgenic mice expressing Reg I.
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.
Yamaoka
T
T
Division of Genetic Information, Institute for Genome Research, University of Tokushima, Japan. yamoaka@genome.tokushima-u.ac.jp
Yoshino
K
K
Yamada
T
T
Idehara
C
C
Hoque
M O
MO
Moritani
M
M
Yoshimoto
K
K
Hata
J
J
Itakura
M
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology; D005260:Female; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D019076:Transgenes
D007328:Insulin; D012333:RNA, Messenger