Localization of Idd11 Is Not Associated With Thymus and NKT Cell Abnormalities in NOD Mice

Localization of Idd11 Is Not Associated With Thymus and NKT Cell Abnormalities in NOD Mice Thomas C. Brodnicki 1 , Anne L. Fletcher 2 , Daniel G. Pellicci 3 , Stuart P. Berzins 3 , Peter McClive 4 , Fiona Quirk 1 , Kylie E. Webster 1 , Hamish S. Scott 1 , Richard L. Boyd 2 , Dale I. Godfrey 3 and Grant Morahan 5 1 Genetics and Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia 2 Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia 3 Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia 4 Department of Pediatrics, The Royal Children’s Hospital, Parkville, Victoria, Australia 5 Diabetes Research Centre, Western Australian Institute for Medical Research, Perth, Australia Address correspondencereprint requests to Thomas C. Brodnicki, The WalterEliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 Australia. E-mail: brodnicki{at}wehi.edu.au Abstract Congenic mouse strains provide a unique resource for genetic dissection and biological characterization of chromosomal regions associated with diabetes progression in the nonobese diabetic (NOD) mouse. Idd11 , a mouse diabetes susceptibility locus, was previously localized to a region on chromosome 4. Comparison of a panel of subcongenic NOD mouse strains with different intervals derived from the nondiabetic C57BL/6 (B6) strain now maps Idd11 to an ∼8-Mb interval. B6-derived intervals protected congenic NOD mice from diabetes onset, even though lymphocytic infiltration of pancreatic islets was similar to that found in NOD mice. In addition, neither thymic structural irregularities nor NKT cell deficiencies were ameliorated in diabetes-resistant congenic NOD mice, indicating that Idd11 does not contribute to these abnormalities, which do not need to be corrected to prevent disease. Footnotes While this manuscript was under review, an article was published that provided additional evidence for the presence of a diabetes susceptibility locus within a region on Chr4 encompassing the Idd11 interval defined here ( 1 ). Additional information for this article can be found in an online appendix available at http://diabetes.diabetesjournals.org . Accepted August 26, 2005. Received June 17, 2005. DIABETES