Studies in humans partially trisomic for HSA21 identified a region whose presence in three copies was sufficient to create many DS phenotypes, including intellectual disability; it was thereby labeled the Down Syndrome Critical Region (DSCR) (Korenberg, 1990; Peterson et al., 1994; Rahmani et al., 1989; Yamamoto et al., 2011). Recent studies in mice carrying all or part of the homologous region of mouse Chromosome 16 have shown that many DS-like phenotypes are linked to genes in this region (Belichenko et al., 2009; Dierssen and de Lagran, 2006; Jiang et al., 2015; Reeves et al., 1995). Within the DSCR, Kcnj6 is a candidate for contributing through increased dose to cognitive deficits. Kcnj6 is present in 3 copies in both people with DS and Ts65Dn mice. This gene encodes the Kir3.2 (Girk2) subunit of inwardly rectifying potassium channels which serve as effectors for a number of postsynaptic metabotropic receptors (Luscher et al., 1997; Mark and Herlitze, 2000; Yamada et al., 1998). As predicted by increased dose, the Kir3.2 product of Kcnj6 is increased in Ts65Dn mice (Harashima et al., 2006; Kleschevnikov et
