Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to theIdd5diabetes susceptibility region

• DOI: 10.1073/pnas.94.16.8670
• Publication Date: 2002-07-26T14:31:44Z
• Authors: Francesco Colucci; Marie-Louise Bergman; Carlos Penha-Gonç...; Corrado M. Cilio; Dan Holmberg
• Keywords: NOD mice; Centimorgan

Defects in lymphocyte apoptosis may lead to autoimmune disorders and contribute the pathogenesis of type 1 diabetes. Lymphocytes nonobese diabetic (NOD) mice, an animal model diabetes, have been found resistant various signals, including alkylating drug cyclophosphamide. Using F2 intercross between apoptosis-resistant NOD mouse apoptosis-susceptible C57BL/6 mouse, we define a major locus controlling apoptosis-resistance phenotype demonstrate its linkage (logarithm odds score = 3.9) group medial markers on chromosome 1. The newly defined gene cannot be dissociated from Ctla4 Cd28 fact marks 20-centimorgan region encompassing Idd5, previously postulated diabetes susceptibility locus. Interestingly, find that CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) CD28 costimulatory molecules are defectively expressed suggesting one or both these involved control resistance and, turn, susceptibility.