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Conditioning the genome identifies additional diabetes resistance loci in Type I diabetes resistant NOR/Lt mice

Genes & Immunity volume 6, pages 528–538 (2005)Cite this article

A Corrigendum to this article was published on 01 March 2006

Abstract

While sharing the H2g7 MHC and many other important Type I diabetes susceptibility (Idd) genes with NOD mice, the NOR strain remains disease free due to resistance alleles within the ∼12% portion of their genome that is of C57BLKS/J origin. Previous F2 segregation analyses indicated multiple genes within the ‘Idd13’ locus on Chromosome 2 provide the primary component of NOR diabetes resistance. However, it was clear other genes also contribute to NOR diabetes resistance, but were difficult to detect in the original segregation analyses because they were relatively weak compared to the strong Idd13 protection component. To identify these further genetic components of diabetes resistance, we performed a new F2 segregation analyses in which NOD mice were outcrossed to a ‘genome-conditioned’ NOR stock in which a large component of Idd13-mediated resistance was replaced with NOD alleles. These F2 segregation studies combined with subsequent congenic analyses confirmed the presence of additional NOR resistance genes on Chr. 1 and Chr. 4, and also potentially on Chr. 11. These findings emphasize the value for diabetes gene discovery of stratifying not only MHC loci conferring the highest relative risk but also as many as possible of the non-MHC loci presumed to contribute significantly.

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Acknowledgements

We gratefully acknowledge the assistance provided by Pamela Stanley, Bruce Regimbal and Steve Langley for animal breeding, and by Gunjan Wagner for assistance with SNP genotyping. This work was supported by NIH Grants DK27722 and DK36175. Institutional shared services were supported by National Cancer Institute Center Support Grant CA-34196.

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Authors and Affiliations

  1. The Jackson Laboratory, Bar Harbor, ME, USA

    P C Reifsnyder, R Li, G Churchill, D V Serreze & E H Leiter

  2. Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia

    P A Silveira

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  1. P C Reifsnyder
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  2. R Li
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  3. P A Silveira
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  4. G Churchill
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Correspondence to E H Leiter.

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Reifsnyder, P., Li, R., Silveira, P. et al. Conditioning the genome identifies additional diabetes resistance loci in Type I diabetes resistant NOR/Lt mice. Genes Immun 6, 528–538 (2005). https://doi.org/10.1038/sj.gene.6364241

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