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Diabetes 56:506-512, 2007
DOI: 10.2337/db06-1027
© 2007 by the American Diabetes Association
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Genetic Reconstitution of Autoimmune Type 1 Diabetes With Two Major Susceptibility Genes in the Rat

Norihide Yokoi1,2, Chihiro Hayashi1, Yuuka Fujiwara1, He-Yao Wang3, and Susumu Seino1

1 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
2 Clinical Genome Informatics Center, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan
3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Address correspondence and reprint requests to Susumu Seino, Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan. E-mail: seino{at}med.kobe-u.ac.jp

Abbreviations: MHC, major histocompatibility complex; SPF, specific pathogen free

The Komeda diabetes-prone (KDP) rat is an animal model of human autoimmune type 1 diabetes. We have previously shown that two major susceptibility genes, the major histocompatibility complex (MHC) RT1u haplotype and Cblb (Casitas B-lineage lymphoma b) mutation, are responsible for the development of diabetes in KDP rats, suggesting a two-gene model for development of the disease. To confirm the two-gene model, we produced a congenic strain carrying mutated Cblb alleles of the KDP rat on a non-KDP genetic background harboring the RT1u haplotype on its MHC. Despite the low incidence and delayed onset of diabetes, the congenic strain did develop the disease, indicating that type 1 diabetes can be reconstituted on a non-KDP genetic background with the RT1u haplotype and Cblb mutation. Similar to observations in KDP rats, the congenic strain showed insulitis and thyroiditis, symptoms of autoimmunity. The low incidence and delayed onset of the disease strongly suggest involvement of genetic modifiers; the congenic strain established in this study should be useful for the mapping and identification of such modifiers.


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2007 by the American Diabetes Association.