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Genetic analysis of the LEW.1AR1-iddm rat: an animal model for spontaneous diabetes mellitus

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Abstract

The LEW.1AR1-iddm/Ztm rat is a new animal model of type 1 diabetes mellitus, which shows an autosomal recessive mode of inheritance for the diabetes-inducing gene. The aim of this study was to define predisposing loci of the diabetic syndrome by linkage analysis using microsatellite markers. A backcross population of 218 rats (BN × LEW.1AR1-iddm) × LEW.1AR1-iddm was analyzed using 157 polymorphic microsatellite markers covering the entire genome. Three genomic regions showed a significant linkage to the diabetic syndrome. The first susceptibility locus on rat Chromosome (RNO) 1 (LOD score 4.13) mapped to the region 1q51–55, which codes for potential candidate genes like Ins1 and Nkx2-3. The second susceptibility locus was also localized on RNO1 in the centromeric region 1p11 (LOD score 2.7) encompassing the Sod2 gene. The third quantitative trait loci (LOD score 2.97) was located on RNO20 within the major histocompatibility complex region. Comparative mapping revealed that the homologous regions in the human genome contain the IDDM loci 1, 5, 8, and 17. The identification of diabetes susceptibility regions of the genetically uniform LEW.1AR1-iddm rat strain will pave the way toward a detailed characterization of the loci conferring diabetes development as well as their functional relevance for the pathogenesis of type 1 diabetes mellitus.

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Acknowledgments

H.W. is a graduate student in the Graduate Research Training Programme No. 705 funded by the Deutsche Forschungsgemeinschaft. This work was supported by a grant from the Deutsche Forschungsgemeinschaft to A.J. and by an NIH grant 1R21AI55464-01 to S.L. and H.J.H. The author thank S.L. Guenet, X. Montagutelli, and K.W. Broman for excellent statistical advice. The technical assistance of M. Meyer, S. Eghtessadi, I. Trotz, and S. Przyklenk is gratefully acknowledged.

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Authors and Affiliations

  1. Institute of Clinical Biochemistry, Hannover Medical School, 30623, Hannover, Germany

    Heike Weiss, Matthias Elsner, Sigurd Lenzen & Markus Tiedge

  2. Institute of Laboratory Animal Science, Hannover Medical School, 30623, Hannover, Germany

    Heike Weiss, Andre Bleich, Hans-Jürgen Hedrich, Anne Jörns & Dirk Wedekind

  3. Institute of Neuropathology, University of Bonn, 53105, Bonn, Germany

    Bernd Kölsch

  4. Centre of Anatomy, Hannover Medical School, 30623, Hannover, Germany

    Anne Jörns

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  1. Heike Weiss
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  2. Andre Bleich
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Correspondence to Dirk Wedekind.

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Weiss, H., Bleich, A., Hedrich, HJ. et al. Genetic analysis of the LEW.1AR1-iddm rat: an animal model for spontaneous diabetes mellitus. Mamm Genome 16, 432–441 (2005). https://doi.org/10.1007/s00335-004-3022-8

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