Document Type
Article
Publication Date
4-1-2009
Description
OBJECTIVE-Two type 1 diabetes susceptibility genes have been identified in the spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major histocompatibility complex (MHC) (RT1) class II u haplotype (Iddm1) and Gimap5 (Iddm2). The strong effects of these have impeded previous efforts to map additional loci. We tested the hypothesis that type 1 diabetes is a polygenic disease in the BBDP rat. RESEARCH DESIGN AND METHODS-We performed the most comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease onset (AOO), and insulitis subpheno- types in 574 F2 animals from a cross-intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP- RT1u,Gimap5 (ACI.BB 1ulyp) rats, where both Iddm1 and Iddm2 were fixed as BBDP. RESULTS-A total of 19% of these F2 animals developed type 1 diabetes, and eight type 1 diabetes susceptibility loci were mapped, six showing significant linkage (chromosomes 1, 3, 6 [two loci], 12, and 14) and two (chromosomes 2 and 17) suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to the severity of islet infiltration by immunocytes, while those on chromosomes 1, 6 (two loci), 14, 17, and a type 1 diabetes-unlinked chromosome 8 interval showed significant linkage to the degree of islet atrophy. Four loci exhibited suggestive linkage to AOO on chromosomes 2 (two loci), 7, and 18 but were unlinked to type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30, associated with human type 1 diabetes, are contained within the chromosomes 1, 2, 7, and 12 loci. CONCLUSIONS-This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes.
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This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Citation Information
Wallis, Robert H.; Wang, Kesheng; Marandi, Leili; Hsieh, Eugene; Ning, Terri; Chao, Gary Y.C.; Sarmiento, Janice; Paterson, Andrew D.; and Poussier, Philippe. 2009. Type 1 Diabetes in the BB Rat: A Polygenic Disease. Diabetes. Vol.58(4). 1007-1017. https://doi.org/10.2337/db08-1215 PMID: 19168599 ISSN: 0012-1797
Copyright Statement
© 2009 by the American Diabetes Association. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .