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

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.

Moderate hyperglycemia suppresses melanoma metastasis to liver

“…GKKO mice were previously developed by systemic heterozygous knockout of glucokinase ( Gk ) and registered as B6; 129- Gckt m1Tms [ 15 ]. Normal littermates of GKKO mice were used as the control wild-type mice (Wild mice).…”

“…To proceed with this study, a pre-diabetes model was essential. Pre-diabetes model mice are gene-modified mice developed by heterozygous knockout of glucokinase ( Gk ) gene (GKKO mice) and show a deficiency in glucose-stimulated insulin secretion (GSIS) [ 15 , 16 ]. GKKO mice stably exhibit moderate blood glucose levels under normal diet conditions and appear to be diabetic once fed with a high-fat diet, though by adjusting the feeding period or reversing the feed type, blood glucose levels are reversible.…”

“…m1Tms (http://ilarlabcode. nas.edu/search_codes_full.php?labcode_id=9447&user_ id=57616)[15]. Normal littermates of 5 and No.…”

Functional role of natural killer T cells in non-obese pre-diabetes model mice

“…The pre-diabetes model mice were those previously developed by systemic heterozygous knockout of Gk and registered as B6;129-Gckt m1Tms (http://ilarlabcode. nas.edu/search_codes_full.php?labcode_id=9447&user_ id=57616) (Saito et al 2015), and here designated as G-mice. Normal littermates of the pre-diabetes model mice were used as the control wild mice (W-mice).…”

“…According to the method described by Bali et al (1995) we formerly established a novel mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene (Gk) (Saito et al 2015). To characterize this strain, the glucose tolerance test was conducted with a series of strains with backcross numbers of 5-10.…”