Production of a mouse strain with impaired glucose tolerance by systemic          heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes          model

Mikako SAITO; Asako KANEDA; Tae SUGIYAMA; Ryousuke IIDA; Keiko OTOKUNI; Misako KABURAGI; Hideaki MATSUOKA

doi:10.1538/expanim.14-0089

Originals

Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model

Mikako SAITO, Asako KANEDA, Tae SUGIYAMA, Ryousuke IIDA, Keiko OTOKUNI, Misako KABURAGI, Hideaki MATSUOKA

Author information

Mikako SAITO
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Asako KANEDA
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Tae SUGIYAMA
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Ryousuke IIDA
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Keiko OTOKUNI
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Misako KABURAGI
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Hideaki MATSUOKA
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan

Keywords: glucokinase, glucose tolerance test, high-fat diet, prediabetes model mouse, systemic heterozygous knockout

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Supplementary material

2015 Volume 64 Issue 3 Pages 231-239

DOI https://doi.org/10.1538/expanim.14-0089

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Abstract

Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk^+/−) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk^+/− mice ranged from 0.41–0.68 versus that in wild (Gk^+/+) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk^+/− strain fed the CD, and Gk^+/− strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk^+/− strain developed in this study.

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