Identification of epistatic interaction involved in obesity using the KK/Ta mouse as a type 2 diabetes model -: Is Zn-α2 glycoprotein-1 a candidate gene for obesity?

被引:53
作者
Gohda, T [1 ]
Makita, Y [1 ]
Shike, T [1 ]
Tanimoto, M [1 ]
Funabiki, K [1 ]
Horikoshi, S [1 ]
Tomino, Y [1 ]
机构
[1] Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol,Bunkyo Ku, Tokyo 1138421, Japan
关键词
D O I
10.2337/diabetes.52.8.2175
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The KK/Ta strain serves as a suitable polygenic mouse model for the common form of type 2 diabetes associated with obesity in humans. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In this study, we focused on expression in the kidneys and liver of KK/Ta and BALB/c mice using differential display (DD) PCR. Zn-alpha(2) glycoprotein-1 (Azgp1) mRNA levels were increased in the kidneys and liver in KK/Ta mice, and sequence analysis revealed a missense mutation. We analyzed the relationship between this polymorphism and various phenotypes in 208 KK/Ta X (BALB/c X KK/Ta) F1 backcross mice. Statistical analysis revealed that Azgp1 and D17Mit218 exhibit a suggestive linkage to body weight (8 weeks) (logarithm of odds 2.3 and 2.9, respectively). Moderate gene-gene interactions were observed at these loci. Adiponectin mRNA levels in 3T3-L1 cells transfected with the expression pcDNA 3.1 vector containing Azgp1 coding sequence of KK/Ta mice were significantly higher than those of BALB/c mice. These results suggest that Azgp1 is a possible candidate gene for regulation of body weight, elucidation of polygenic inheritance, and age-dependent changes in the genetic control of obesity.
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页码:2175 / 2181
页数:7
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