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Experimental Diabetes Research
Volume 2012 (2012), Article ID 582546, 6 pages
Review Article

Genetic Dissection of Complex Genetic Factor Involved in NIDDM of OLETF Rat

1Laboratory of Animal Genetics, Division of Life and Food Sciences, Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan
2Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan
3Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka 569-1125, Japan
4Department of Laboratory Animal Science, Faculty of Integrated Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan

Received 4 September 2012; Accepted 20 September 2012

Academic Editor: Tomohiko Sasase

Copyright © 2012 Takahisa Yamada 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.


The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, noninsulin-dependent diabetes mellitus (NIDDM) in humans. NIDDM in this rat model was shown to be regulated by multiple genes. We have identified 14 quantitative trait loci (QTLs) responsible for NIDDM (Nidd1-14/of) on chromosomes 1, 5, 7, 8, 9, 11, 12, 14, 16, and 17 by a whole genome search in 160 F2 progenies obtained by mating the OLETF and the F344 rats. Among these loci, two QTLs, Nidd1 and 2/of, were declared significant loci at a genome-wide level. Nidd3, 8, 9, and 13/of exhibited heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between Nidd1/of and Nidd2/of, between Nidd1/of and Nidd10/of, between Nidd2/of and Nidd8/of, and between Nidd2/of and Nidd14/of. Furthermore, Nidd6 and 11/of showed linkage with body weight, and Nidd1, 2, 8, 9, 10, and 12/of had an interaction with body weight. These indicated that NIDDM in the OLETF would have a higher degree of genetic complexity. We suggest several interesting candidate genes located in rat genomic regions for Nidd1-14/of or the syntenic regions in human genome.