Sequence Analysis of Candidate Genes for Common Susceptibility to Type 1 and Type 2 Diabetes in Mice.

Yamada, Kazunori; Ikegami, Hiroshi; Kawaguchi, Yoshihiko; Fujisawa, Tomomi; Hotta, Mizuo; Ueda, Hironori; Shintani, Maki; Nojima, K.; Kawabata, Yumiko; Ono, Masaya; Nishino, Masanori; Itoi, Michiko; Babaya, Naru; Shibata, Masao; Makino, Susumu; Ogihara, Toshio

doi:10.1507/endocrj.48.241

Cited by 6 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported sequence analyses of the genes for hepatocyte nuclear factor-1β, GLUT4 and nucleoredoxin [6,7,[38][39][40]. In this study, we determined the nucleotide sequences of Gck, which is mapped in the centromeric region of Chr11.…”

Section: Discussionmentioning

confidence: 99%

Direct evidence for susceptibility genes for type 2 diabetes on mouse chromosomes 11 and 14

et al. 2010

View full text Add to dashboard Cite

These data provide direct evidence that Chr11 and Chr14 harbour major susceptibility genes for type 2 diabetes. These two chromosomes interact to cause more severe hyperglycaemia and obesity, which was not observed with the presence of either single chromosome, indicating different modes of gene-gene interaction depending on the phenotype. Marked changes in the phenotypes retained in the consomic strains will facilitate fine mapping and the identification of the responsible genes and their interaction with each other, other genes and environmental factors.

show abstract

Section: Discussionmentioning

confidence: 99%

Direct evidence for susceptibility genes for type 2 diabetes on mouse chromosomes 11 and 14

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In addition, the mutation in the HNF1B (HNF1 homeobox B, Tcf2) [22,23] has been identified as the cause of MODY5. We previously reported sequence analyses of Gck [5] and Hnf1b (Tcf2) [4,24,25], which showed allelic variation between NSY and control C3H mice. The Gck gene (5.9 Mb) is located in the R1 and R2 congenic region (segment A in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Based on human GWAS, SGCD, which is a component of the sarcoglycan complex, and JADE2, which acts as an E3 ubiquitin ligase, were suggested as candidate genes for impaired insulin secretion and hyperglycemia in the R2 congenic region (segment B, Additional file 3). We previously reported sequence analyses of other candidate genes for type 2 diabetes on Chr 11 including glucose transporter 4 [26], thioredoxin [25], and nucleoredoxin [27]. Coding sequences of these gene did not have allelic variantion between NSY and C3H mice, suggesting that amino acid substitution in these genes was unlikely to be responsible for type 2 diabetes susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes susceptibility genes on mouse chromosome 11 under high sucrose environment

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Both genetic and environmental factors contribute to type 2 diabetes development. We used consomic mice established from an animal type 2 diabetes model to identify susceptibility genes that contribute to type 2 diabetes development under specific environments. We previously established consomic strains (C3H-Chr 11 NSY and C3H-Chr 14 NSY) that possess diabetogenic Chr 11 or 14 of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes, in the genetic background of C3H mice. To search genes contribute to type 2 diabetes under specific environment, we first investigated whether sucrose administration deteriorates type 2 diabetesrelated traits in the consomic strains. We dissected loci on Chr 11 by establishing congenic strains possessing different segments of NSY-derived Chr 11 under sucrose administration. Results: In C3H-Chr 11 NSY mice, sucrose administration for 10 weeks deteriorated hyperglycemia, insulin resistance, and impaired insulin secretion, which is comparable to NSY mice with sucrose. In C3H-Chr 14 NSY mice, sucrose administration induced glucose intolerance, but not insulin resistance and impaired insulin secretion. To dissect the gene(s) existing on Chr 11 for sucrose-induced type 2 diabetes, we constructed four novel congenic strains (R1, R2, R3, and R4) with different segments of NSY-derived Chr 11 in C3H mice. R2 mice showed marked glucose intolerance and impaired insulin secretion comparable to C3H-Chr 11 NSY mice. R3 and R4 mice also showed impaired insulin secretion. R4 mice showed significant decreases in white adipose tissue, which is in the opposite direction from parental C3H-Chr 11 NSY and NSY mice. None of the four congenic strains showed insulin resistance. Conclusions: Genes on mouse Chr 11 could explain glucose intolerance, impaired insulin secretion, insulin resistance in NSY mice under sucrose administration. Congenic mapping with high sucrose environment localized susceptibility genes for type 2 diabetes associated with impaired insulin secretion in the middle segment (26.0-63.4 Mb) of Chr 11. Gene(s) that decrease white adipose tissue were mapped to the distal segment of Chr 11. The identification of diabetogenic gene on Chr 11 in the future study will facilitate precision medicine in type 2 diabetes by controlling specific environments in targeted subjects with susceptible genotypes.

show abstract

“…This suggests the possibility that human orthologues of the diabetes-susceptibility gene(s) on mouse Chr11 are acting as rare variants in humans and therefore have not been detected by genome-wide association studies. Candidate genes on mouse Chr11 are hepatocyte nuclear factor-1 β , GLUT4, nucleoredoxin, and glucokinase [3, 5–7, 18, 19]. Human orthologues of these genes and other candidate genes on Chr11 are important candidates for genes explaining the so-called missing heritability in human type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11

Babaya

Ueda

Noso

et al. 2013

Journal of Diabetes Research

Self Cite

View full text Add to dashboard Cite

The quantitative trait locus (QTL) mapping in segregating crosses of NSY (Nagoya-Shibata-Yasuda) mice, an animal model of type 2 diabetes, with nondiabetic strain C3H/He mice has identified diabetogenic QTLs on multiple chromosomes. The QTL on chromosome 11 (Chr11) (Nidd1n) showing the largest effect on hyperglycemia was confirmed by our previous studies with homozygous consomic mice, C3H-11NSY, in which the NSY-derived whole Chr11 was introgressed onto control C3H background genes. C3H-11NSY mice also showed a streptozotocin (STZ) sensitivity. In the present study, we constructed heterozygous C3H-11NSY mice and the phenotypes were analyzed in detail in comparison with those of homozygous C3H-11NSY and C3H mice. Heterozygous C3H-11NSY mice had significantly higher blood glucose levels and STZ sensitivity than those in C3H mice. Hyperglycemia and STZ sensitivity in heterozygous C3H-11NSY mice, however, were not as severe as in homozygous C3H-11NSY mice. The body weight and fat pad weight in heterozygous C3H-11NSY mice were similar to those in C3H and homozygous C3H-11NSY mice. These data indicated that the introgression of Chr11 of the diabetes-susceptible NSY strain onto diabetes-resistant C3H caused marked changes in the glucose tolerance and STZ susceptibility even in a heterozygous state, and suggested that the mode of inheritance of a gene or genes on Chr11 for hyperglycemia and STZ sensitivity is additive.

show abstract

Sequence Analysis of Candidate Genes for Common Susceptibility to Type 1 and Type 2 Diabetes in Mice.

Cited by 6 publications

References 30 publications

Direct evidence for susceptibility genes for type 2 diabetes on mouse chromosomes 11 and 14

Direct evidence for susceptibility genes for type 2 diabetes on mouse chromosomes 11 and 14

Type 2 diabetes susceptibility genes on mouse chromosome 11 under high sucrose environment

Dose Effect and Mode of Inheritance of Diabetogenic Gene on Mouse Chromosome 11

Contact Info

Product

Resources

About