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- Title
Identification of epistatic interaction involved in obesity using the KK/Ta mouse as a Type 2 diabetes model: is Zn-alpha2 glycoprotein-1 a candidate gene for obesity?
- Authors
Gohda, Tomohito; Makita, Yuichiro; Shike, Toshihide; Tanimoto, Mitsuo; Funabiki, Kazuhiko; Horikoshi, Satoshi; Tomino, Yasuhiko
- Abstract
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.
- Subjects
TYPE 2 diabetes; OBESITY; KIDNEY diseases; LIVER diseases; KIDNEY physiology; LIVER physiology; RNA metabolism; AMINO acids; ANIMALS; BIOLOGICAL models; BODY weight; CHROMOSOMES; DIABETES; DOCUMENTATION; GENE expression; GENES; GROWTH factors; MICE; GENETIC mutation; PROTEINS; TRIGLYCERIDES; TUMOR necrosis factors; PHENOTYPES; ADIPONECTIN
- Publication
Diabetes, 2003, Vol 52, Issue 8, p2175
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.52.8.2175