In rodents, Kir3.2 is present in the neocortex, cerebellum, hippocampus, and thalamus as early as p5 (Fernandez-Alacid et al., 2011; Liesi et al., 2000). In the DS brain, Kir3.2 was detected at both 17 and 33 weeks of gestation (Thiery et al., 2003). Thus, increased Kcnj6 gene dose and its Kir3.2 protein product could contribute to changes in brain function in both mouse models and people with DS as early as the developmental period. In adult Ts65Dn mice, Kir3.2 is overexpressed in many brain regions, including the neocortex and hippocampus (Harashima et al., 2006; Kleschevnikov et al., 2012b; Kleschevnikov et al., 2005). This change results in increased GABAB/Kir3.2 signaling, which plays a defining role in the increased inhibition observed in Ts65Dn mice (Best et al., 2012; Best et al., 2007; Deidda et al., 2015; Kleschevnikov et al., 2012b; Kleschevnikov et al., 2004; Mojabi et al., 2016).
