Localization of Idd11 using NOD congenic mouse strains: elimination of Slc9a1 as a candidate gene.
Type 1 diabetes is a multigenic autoimmune disease, the genetic basis for which is perhaps best characterized in the nonobese diabetic (NOD) mouse model. We previously located a NOD diabetes susceptibility locus, designated Idd11, on mouse Chromosome (Chr) 4 by analyzing diabetic backcross mice produced after crossing NOD/Lt with the nondiabetic resistant strain C57BL/6 (B6) strain. In order to confirm Idd11 and further refine its location, three NOD congenic mouse strains with different B6 derived intervals within Chr 4 were generated. Two of the congenic strains had a significant decrease in the cumulative incidence of diabetes compared with NOD/Lt control mice. The third NOD congenic strain, containing a B6 interval surrounding the Slc9a1 locus, was not protected against diabetes. These results define a new distal boundary for Idd11 and eliminate the Slc9a1 gene as a candidate. The Idd11 locus has now been definitively mapped to a 13cM interval on mouse Chr 4.
Brodnicki
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Genetics and Bioinformatics Group, The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.
McClive
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Couper
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Morahan
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D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015994:Incidence; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010641:Phenotype; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*
D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1