Cognitive and pharmacological insights from the Ts65Dn mouse model of Down syndrome

Down syndrome (DS) is a multi-faceted condition resulting in the most common genetic form of intellectual disability. Mouse models of DS, especially the Ts65Dn model, have been pivotal in furthering our understanding of the genetic, molecular and neurobiological mechanisms that underlie learning and memory impairments in DS. Cognitive and pharmacological insights from the Ts65Dn mouse model have led to remarkable translational progress in the development of therapeutic targets and in the emergence of DS clinical trials. Unravelling the pathogenic role of trisomic genes on human chromosome 21 and the genotype-phenotype relationship still remains a pertinent goal for tackling cognitive deficits in DS.

► DS causes perturbed synaptic plasticity and excessive inhibitory neurotransmission. ► Ts65Dn mouse model recapitulates behavioural and cognitive phenotypes of DS. ► Several triplicated Hsa21-associated genes in Ts65Dn mice are implicated. ► Insights from Ts65Dn have led to pharmacological interventions and clinical trials.