Mouse genetic models of DS provide an opportunity to investigate the neurobiology of DS (Belichenko et al., 2015; Das and Reeves, 2011; Edgin et al., 2012; Gardiner et al., 2003; Mojabi et al., 2016; Reeves et al., 1995; Rueda et al., 2012; Yu et al., 2010) and to explore the role of individual genes in DS phenotypes (Altafaj et al., 2013; Salehi et al., 2006). Similar to DS, mouse genetic models of DS exhibit deficient hippocampus-dependent long-term memory, working memory, and other physiological and behavioral changes consistent with deficits in cognition (Fernandez et al., 2007). Mouse models that contain different as well as overlapping sets of triplicated genes have been genetically engineered and examined to explore phenotype-genotype relationship (Davisson et al., 1990; Jiang et al., 2015; O’Doherty et al., 2005; Olson et al., 2004a; Pereira et al., 2009; Sago et al., 1998; Yu et al., 2010). The most intensively investigated mouse is the Ts65Dn model, whose creation 26 years ago was instrumental in advancing this field of study (Davisson et al., 1990). Ts65Dn mice exhibit many phenotypes characteristic of DS
