Down’s syndrome is a genetic disorder caused by duplication of human chromosome 21, which contains the Girk2 (Kcnj6) gene. To investigate the contribution of a third copy of the Girk2 gene to the phenotype of Down’s syndrome, two mouse models have been generated that carry either a partial or full segment duplication of the mouse chromosome 16, the ortholog to human chromosome 21149,150. In both lines, GIRK2 protein is upregulated, resulting in a larger slow IPSC mediated by GABAB receptors151. Moreover, hippocampal LTP is reduced while LTD is enhanced in both lines and therefore synaptic plasticity of glutamatergic transmission is altered. Since the duplicated chromosomal segment also carries other genes, additional studies are needed to specifically test the role of GIRK channels in the malfunction of the nervous system in Down’s syndrome.
