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ABSTRACT While sharing the _H2__g7_ 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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Scholar  Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The Jackson Laboratory, Bar Harbor, ME, USA P C Reifsnyder, R Li, G Churchill, D V Serreze & E H Leiter * Centenary Institute of

Cancer Medicine and Cell Biology, Newtown, NSW, Australia P A Silveira Authors * P C Reifsnyder View author publications You can also search for this author inPubMed Google Scholar * R Li

View author publications You can also search for this author inPubMed Google Scholar * P A Silveira View author publications You can also search for this author inPubMed Google Scholar * G

Churchill View author publications You can also search for this author inPubMed Google Scholar * D V Serreze View author publications You can also search for this author inPubMed Google

Scholar * E H Leiter View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to E H Leiter. RIGHTS AND PERMISSIONS Reprints

and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 21 December 2004 * Revised: 06 June 2005 * Accepted: 07 June

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KEYWORDS * mice * diabetes * autoimmunity * genetics * NOD