TY - JOUR
T1 - Production and characterization of Reg knockout mice
T2 - Reduced proliferation of pancreatic β-cells in Reg knockout mice
AU - Unno, Michiaki
AU - Nata, Koji
AU - Noguchi, Naoya
AU - Narushima, Yoichi
AU - Akiyama, Takako
AU - Ikeda, Takayuki
AU - Nakagawa, Kei
AU - Takasawa, Shin
AU - Okamoto, Hiroshi
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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.
AB - 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.
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U2 - 10.2337/diabetes.51.2007.s478
DO - 10.2337/diabetes.51.2007.s478
M3 - Article
C2 - 12475793
AN - SCOPUS:0036894357
VL - 51
SP - S478-S483
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - SUPPL. 3
ER -