Diabetes 51:S478-S483, 2002
© 2002 by the American Diabetes Association, Inc.
Section 6: Beta-Cell Survival |
Production and Characterization of Reg Knockout Mice
Reduced Proliferation of Pancreatic ß-Cells in Reg Knockout Mice
Michiaki Unno,
Koji Nata,
Naoya Noguchi,
Yoichi Narushima,
Takako Akiyama,
Takayuki Ikeda,
Kei Nakagawa,
Shin Takasawa, and
Hiroshi Okamoto
From the Department of Biochemistry, Tohoku University Graduate School of Medicine, Miyagi, Japan
Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated in vitro and in vivo that the exogenous addition of rat and human Reg gene products, Reg/REG proteins, induced ß-cell replication via the Reg receptor and thereby ameliorated experimental diabetes. In the present study, we produced Reg knockout mice by homologous recombination. The Reg gene disruption resulted in a null mutation. Knockout mice developed normally. Islets from the Reg knockout mice appeared morphologically indistinguishable from those of normal controls. However, [3H]thymidine incorporation in isolated islets from Reg knockout mice was decreased. When hyperplastic islets were induced by the injection of goldthioglucose, the average islet size in Reg knockout mice was significantly smaller than that of control Reg+/+ mice. We then produced transgenic mice carrying the Reg gene under the control of the rat insulin II promoter (Ins-Reg) to express Reg in ß-cells. Isolated islets from the Ins-Reg transgenic mice showed increased [3H]thymidine incorporation. By intercrossing, we produced NOD mice carrying the Ins-Reg transgene and found that development of diabetes in the resultant Ins-Reg transgenic NOD mice was significantly retarded, coinciding with an increase in the pancreatic ß-cell mass. These results indicate that Reg plays an important role in ß-cell growth/regeneration.

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Copyright © 2002 by the American Diabetes Association.
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