title: Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse.
abstract: T1D (Type 1 diabetes) is an autoimmune disease caused by the immune-mediated destruction of pancreatic β-cells. Studies in T1D patients have been limited by the availability of pancreatic samples, a protracted pre-diabetic phase and limitations in markers that reflect β-cell mass and function. The NOD (non-obese diabetic) mouse is currently the best available animal model of T1D, since it develops disease spontaneously and shares many genetic and immunopathogenic features with human T1D. Consequently, the NOD mouse has been extensively studied and has made a tremendous contribution to our understanding of human T1D. The present review summarizes the key lessons from NOD mouse studies concerning the genetic susceptibility, aetiology and immunopathogenic mechanisms that contribute to autoimmune destruction of β-cells. Finally, we summarize the potential and limitations of immunotherapeutic strategies, successful in NOD mice, now being trialled in T1D patients and individuals at risk of developing T1D.
authors.affiliation: Department of Immunology, Monash University, Alfred Hospital Medical Research & Education Precinct (AMREP), Melbourne, VIC 3004, Australia.
authors.forename: Abhirup
authors.initials: A
authors.lastname: Jayasimhan
authors.forename: Kristy P
authors.initials: KP
authors.lastname: Mansour
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Slattery
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D020022:Genetic Predisposition to Disease; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD