Down syndrome (DS), caused by products of the genes that are localized to the extra copy of chromosome 21, is characterized by a complex neurological phenotype that includes mental retardation and motor deficits. Trisomy Ts65Dn mouse is a genetic model of DS because of the presence of a segment derived from mouse chromosome 16 that contains more than a hundred genes orthologous to human chromosome 21 genes. It has been shown that these gene products in Ts65Dn mouse lead to abnormalities that could be referred to DS specific phenotype. The cerebellum is one of the structures that is particularly impacted by these gene products and one of these genes, GIRK2 (inward rectifying potassium channel subunit), has been found to be expressed abundantly in the cerebellum. In this study for the first time we report that GIRK2 is expressed in excitatory interneurons, also known as unipolar brush cells (UBCs) because of their morphological features. We also found that GIRK2 specific immunohistochemical signal in UBCs of Ts65Dn vestibulocerebellum and dorsal cochlear nucleus was significantly stronger that GIRK2 positive signal detected in littermate diploids. Analysis of Disomic-Ts65Dn/GIRK2 (+/+/-) and Heterozygous-diploid/GIRK2 (+/-) that were generated from Ts65Dn and GIRK2 knockout mice shows that GIRK2 expression in UBCs follows a gene dosage. Abnormal overexpression of GIRK2 might affect cerebellar circuitry in Ts65Dn vestibulocerebellum and dorsal cochlear nucleus through GIRK2 effect on somatic membrane potential (high expression level) and to lesser degree its shunting properties in the dendritic region (small expression level).
