title: Thinking bedside at the bench: the NOD mouse model of T1DM.
abstract: Studies over the past 35 years in the nonobese diabetic (NOD) mouse have shown that a number of agents can prevent or even reverse type 1 diabetes mellitus (T1DM); however, these successes have not been replicated in human clinical trials. Although some of these interventions have delayed disease onset or progression in subsets of participants, none have resulted in a complete cure. Even in the most robust responders, the treatments do not permanently preserve insulin secretion or stimulate the proliferation of β cells, as has been observed in mice. The shortfalls of translating NOD mouse studies into the clinic questions the value of using this model in preclinical studies. In this Perspectives, we suggest how immunological and genetic differences between NOD mice and humans might contribute to the differential outcomes and suggest ways in which the mouse model might be modified or applied as a tool to develop treatments and improve understanding of clinical trial outcomes.
authors.affiliation: Department of Immunobiology, 300 George Street, #353E, New Haven, CT 06520, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Reed
authors.affiliation: Department of Immunobiology, Department of Internal Medicine, Yale University, 300 George Street, #353E, New Haven, CT 06520, USA.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D057170:Translational Research, Biomedical; D016896:Treatment Outcome