PT  - JOURNAL ARTICLE
AU  - Ueda, H
AU  - Ikegami, H
AU  - Kawaguchi, Y
AU  - Fujisawa, T
AU  - Yamato, E
AU  - Shibata, M
AU  - Ogihara, T
TI  - Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex trait.
AID  - 10.2337/diabetes.48.5.1168
DP  - 1999 May 01
TA  - Diabetes
PG  - 1168--1174
VI  - 48
IP  - 5
4099  - http://diabetes.diabetesjournals.org/content/48/5/1168.short
4100  - http://diabetes.diabetesjournals.org/content/48/5/1168.full
SO  - Diabetes1999 May 01; 48
AB  - Type 2 diabetes is a complex trait with both genes and environmental factors contributing to susceptibility. Except for rare subtypes with monogenic inheritance, the genetic basis of type 2 diabetes is unknown because of the complex and heterogeneous nature of the disease. By using the NSY mouse, an inbred mouse model of type 2 diabetes, we genetically dissected late-onset type 2 diabetes and demonstrated age-dependent changes in the genetic control of type 2 diabetes as well as polygenic inheritance. Three major loci (Nidd1nsy, Nidd2nsy, Nidd3nsy) were mapped on mouse chromosomes (Chr) 11, 14, and 6, respectively. The existence of a fourth locus (Nidd4nsy) with an age-dependent effect was suggested by longitudinal, but not cross-sectional, analysis of linkage data. Nidd1nsy and Nidd4nsy appear to affect insulin secretion, whereas Nidd2nsy and Nidd3nsy appear to affect insulin sensitivity. A locus on Chr 6 was significantly linked to epididymal fat weight. A candidate disease gene (Tcf2) on Chr 11, encoding hepatic nuclear factor-1beta, was shown to have a rare sequence variant in the DNA binding domain in the model. The mouse model we used will serve as a useful model for future studies on the etiology of late-onset polygenic type 2 diabetes in humans.