A Researcher’s guide to rodent models of Down syndrome: Recent insights and translational perspectives

Summary: Rodent models of Down syndrome (DS) have been transformative in identifying basic mechanisms underlying the effects of Trisomy 21 at the molecular, cellular, physiological, and neurobehavioral levels. Each model, with its unique genomic architecture, has advanced our understanding of the complex multisystem etiology of DS. The availability of multiple models necessitates the challenge of selecting appropriate models to address a particular scientific question, experimental design, and translational relevance. This primer guides the reader through the various rodent models of DS and the genomic and phenotypic effects they recapitulate. We also provide recommendations and strategies for using DS rodent models to enable effective and robust forward and reverse translational approaches.