Genetic dissection of susceptibility genes for diabetes and related phenotypes on mouse chromosome 14 by means of congenic strains

BMC Genetics

Hiroshi Ikegami¹  Tomomi Fujisawa²  Misato Kobayashi³  Michiko Itoi-Babaya²  Yoshihisa Hiromine¹  Shinsuke Noso¹  Hironori Ueda⁴  Naru Babaya¹ 

[1] Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama 589-8511, Osaka, Japan;Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan;Department of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Aichi, Japan;Department of Molecular Endocrinology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan

关键词: Insulin resistance;    Consomic strain;    Complex trait;    Animal model;    Adiposity;   

Others  :  1085690
DOI  :  10.1186/s12863-014-0093-8

 received in 2014-03-17, accepted in 2014-08-14,  发布年份 2014

【 摘 要 】

Background

A susceptibility locus, Nidd2n, for type 2 diabetes has been mapped to mouse chromosome 14 (Chr 14) and confirmed using the consomic strain (C3H-Chr 14^NSY) of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes. The aim of this study was to localize and characterize Nidd2n.

Results

We constructed two novel congenic strains homozygous for different segments of NSY-Chr 14 on the control C3H/HeNcrj (C3H) background: R1 (C3H.NSY-(D14Mit206-D14Mit5)) possesses the proximal and middle segment, and R2 (C3H.NSY-(D14Mit206-D14Mit186)) possesses the most proximal segment of NSY-Chr 14. Diabetes-related phenotypes were studied in comparison with those of consomic C3H-Chr 14^NSY (R0) and parental NSY and C3H strains. Congenic R1 and R2 showed significantly higher post-challenge glucose than that in C3H mice. Fasting glucose, in contrast, was significantly lower in R1 and R2 than in C3H mice. Insulin sensitivity was significantly impaired in R1 and R2 compared to C3H mice. R2 showed significantly higher body weight and fat-pad weight than those in C3H and R1. Leptin level was significantly higher in R0, R1 and R2 than in C3H mice, with R2 showing the highest level, similar to that in NSY mice. Serum adiponectin level was significantly lower in R0, R1 and R2 than in C3H mice, while it was significantly higher in NSY than in C3H mice.

Conclusions

These data indicate that Chr 14 harbors multiple genes for diabetes-related phenotypes. The original Nidd2n, which is located in the middle region of Chr 14, was divided into two segments; Nidd2.1n in proximal Chr 14 and Nidd2.2n in distal Chr 14. Nidd2.1n contributes to post-challenge hyperglycemia, insulin resistance and adiposity. Nidd2.2n contributes to fasting as well as post-challenge hyperglycemia and insulin resistance. Adp1n, which contributes to decreased adiposity and increased insulin sensitivity, rather than a diabetogenic gene, was mapped in the middle segment.

【 授权许可】

   
2014 Babaya et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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Figure 4.

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