NOD mice have distinct metabolic and immunologic profiles when compared with genetically similar MHC-matched ICR mice

Nonobese diabetic (NOD) mice are the most commonly used rodent model to study mechanisms relevant to the autoimmunity and immunology of type 1 diabetes. Although many different strains of mice have been used as controls for studies comparing nondiabetic lines to the NOD strain, we hypothesized that the parental strain that gave rise to the NOD line might be one of the best options. Therefore, we compared female ICR and NOD mice, which are matched at key major histocompatibility complex (MHC) loci, to understand their metabolic and immunologic similarities and differences. Several novel observations emerged: 1) NOD mice have greater circulating proinsulin when compared with ICR mice. 2) NOD mice display CD3+ and IBA1+ cell infiltration into and near pancreatic islets before hyperglycemia. 3) NOD mice show increased expression of the Il1b and Cxcl11 genes in islets when compared with islets from age-matched ICR mice. 4) NOD mice have a greater abundance of STAT1 and ICAM-1 protein in islets when compared with ICR mice. These data show that ICR mice, which are genetically similar to NOD mice, do not retain the same immunologic outcomes. Thus, ICR mice are an excellent choice as a genetically similar and MHC-matched control for NOD mice in studies designed to understand mechanisms relevant to autoimmune-mediated diabetes onset as well as novel therapeutic interventions.NEW & NOTEWORTHY Nonobese diabetic (NOD) mice have more proinsulin in circulation and STAT1 protein in islets compared with the major histocompatibility complex (MHC)-matched ICR line. NOD mice also display greater expression of cytokines and chemokines in pancreatic islets consistent with immune cell infiltration before hyperglycemia when compared with age-matched ICR mice. Thus, ICR mice represent an excellent control for autoimmunity and inflammation studies using the NOD line of mice.