title: 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.
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Saito
authors.forename: Asako
authors.initials: A
authors.lastname: Kaneda
authors.forename: Tae
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Iida
authors.forename: Keiko
authors.initials: K
authors.lastname: Otokuni
authors.forename: Misako
authors.initials: M
authors.lastname: Kaburagi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005091:Exons / Q000235:genetics; D005240:Feasibility Studies; D017353:Gene Deletion; D015870:Gene Expression; D055786:Gene Knockout Techniques / Q000379:methods*; D005941:Glucokinase / Q000235:genetics* / Q000378:metabolism; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D006579:Heterozygote; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics*; D011236:Prediabetic State / Q000235:genetics
chemical_list: D001786:Blood Glucose; D005941:Glucokinase