Production and characterization of Reg knockout mice: Reduced proliferation of pancreatic β-cells in Reg knockout mice

Michiaki Unno, Koji Nata, Naoya Noguchi, Yoichi Narushima, Takako Akiyama, Takayuki Ikeda, Kei Nakagawa, Shin Takasawa, Hiroshi Okamoto

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95 Citations (Scopus)


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 β-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 β-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 β-cell mass. These results indicate that Reg plays an important role in β-cell growth/regeneration.

Original languageEnglish
Pages (from-to)S478-S483
Issue numberSUPPL. 3
Publication statusPublished - 2002 Dec 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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