title: Congenic mapping identifies a novel Idd9 subregion regulating type 1 diabetes in NOD mice.
abstract: Type 1 diabetes (T1D) results from complex interactions between genetic and environmental factors. The nonobese diabetic (NOD) mouse develops spontaneous T1D and has been used extensively to study the genetic control of this disease. T1D is suppressed in NOD mice congenic for the C57BL/10 (B10)-derived Idd9 resistance region on chromosome 4. Previous studies conducted by other investigators have identified four subregions (Idd9.1, Idd9.2, Idd9.3, and Idd9.4) where B10-derived genes suppress T1D development in NOD mice. We independently generated and characterized six congenic strains containing B10-derived intervals that partially overlap with the Idd9.1 and Idd9.4 regions. T1D incidence studies have revealed a new B10-derived resistance region proximal to Idd9.1. Our results also indicated that a B10-derived gene(s) within the Idd9.4 region suppressed the diabetogenic activity of CD4 T cells and promoted CD103 expression on regulatory T cells indicative of an activated phenotype. In addition, we suggest the presence of a B10-derived susceptibility gene(s) in the Idd9.1/Idd9.4 region. These results provide additional information to improve our understanding of the complex genetic control by the Idd9 region.
authors: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
authors: Bixuan
authors: B
authors: Lin
authors: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
authors: Ashley E
authors: AE
authors: Ciecko
authors: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.|Southern Illinois University School of Medicine, Springfield, IL, 62702, USA.
authors: Erin
authors: E
authors: MacKinney
authors: The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
authors: David V
authors: DV
authors: Serreze
authors: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. yichen@mcw.edu.
authors: Yi-Guang
authors: YG
authors: Chen
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018124:Receptors, Tumor Necrosis Factor
keywords: Idd9; NOD mouse; Regulatory T cells; Type 1 diabetes