Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2012, Article ID 858121, 5 pages
Research Article

Single Diabetic QTL Derived from OLETF Rat Is a Sufficient Agent for Severe Diabetic Phenotype in Combination with Leptin-Signaling Deficiency

1Department of Life Science, Division of Natural Sciences, International Christian University, Mitaka, Tokyo 181-8585, Japan
2Division for Animal Research Resources, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan
3Laboratory of Animal Genetics, Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan
4Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan

Received 4 September 2012; Accepted 5 November 2012

Academic Editor: Tomohiko Sasase

Copyright © 2012 Hiroyuki Kose et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Obesity has been considered one of the leading causative agents for diseases such as type 2 diabetes, stroke, and heart attack. Due to their complex etiology, establishing auseful animal model is increasingly crucial for better molecular understanding of how obesity influences on disease development. OLETF rat is a spontaneous model of type 2 diabetes. We mapped 14 hyperglycemia QTLs in the genome of the OLETF rat and subsequently generated a panel of congenic strains each possessing OB-R mutation in F344 genetic background. Here we show that one of the loci, Nidd2/of, is highly responsive to obesity. When leptin receptor mutation is introgressed into the Nidd2/of congenic strain, the rat showed hyperglycemia equivalent to that of the parental OLETF rat. This suggests that the Nidd2/of locus has a strong genetic interaction with leptin signaling pathway. Furthermore, when another hyperglycemia QTL Nidd1/of is additionally combined, the strain developed overt diabetes. A single QTL dissected out in spontaneous model normally exerts only mild effect on the quantitative trait, which makes it difficult to clone the gene. Our new model may help not only to identify the causative gene but also to investigate how obesity interacts with a QTL to regulate diabetic traits.