Accession Number : AD1013852


Title :   Disruption of Inhibitory Function in the Ts65Dn Mouse Hippocampus Through Overexpression of GIRK2


Descriptive Note : Technical Report


Corporate Author : Uniformed Services University Of The Health Sciences Bethesda United States


Personal Author(s) : Best,Tyler K


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1013852.pdf


Report Date : 24 Oct 2007


Pagination or Media Count : 162


Abstract : Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein coupled inward rectifying potassium channel subunit 2 (GIRK2). The DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. With the advent of mouse models of Down syndrome (DS) the possibilities to further explore and understand the dysfunctions associated with DS expands. In particular, the basic and cellular neurophysiology can now be achieved in mice, which was not possible in human DS. Such that specific DS dysfunctions can now be separated from the overall disorder and examined in a manner providing interventions directly addressing particular abnormalities. The function of well defined regions and even certain genes within the triplicated chromosome are being understood with greater clarity to the extent that some DS specific phenotypes could be therapeutically ameliorated in the future. For example, the phenotype in a neurofibromatosis mouse model was reversed with pharmacological treatment.


Descriptors :   GENETIC DISEASES , CHROMOSOME ABERRATIONS , CONGENITAL ABNORMALITIES , MENTAL DEFICIENCY , gene expression , hippocampus , mice , receptor sites physiology , synapsis , proteins , neuroscience , pharmacology , CENTRAL NERVOUS SYSTEM


Distribution Statement : APPROVED FOR PUBLIC RELEASE