Abstract
Without a doubt, rodent models have been instrumental in describing pathways that lead to pancreatic β-cell destruction, evaluating potential causes of type 1 diabetes and providing proof-of-principle for the potential of immune-based interventions. However, despite more than two decades of productive research, we are still yet to define an initiating autoantigen for the human disease, to determine the precise mechanisms of β-cell destruction in humans and to design interventions that prevent or cure type 1 diabetes. In this Perspective article, we propose that a major philosophical change would benefit this field, a proposition that is based on evaluation of situations in which rodent models have provided useful guidance and in which they have led to disappointments.
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The authors are indebted to E. Leiter (Jackson Lab, Bar Harbor, United States) for critical reading of the manuscript, for many helpful suggestions and for providing Box 1.
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Roep, B., Atkinson, M. & von Herrath, M. Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes. Nat Rev Immunol 4, 989–997 (2004). https://doi.org/10.1038/nri1502
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