<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Araud, Tanguy</style></author><author><style face="normal" font="default" size="100%">Graw, Sharon</style></author><author><style face="normal" font="default" size="100%">Berger, Ralph</style></author><author><style face="normal" font="default" size="100%">Lee, Michael</style></author><author><style face="normal" font="default" size="100%">Neveu, Estele</style></author><author><style face="normal" font="default" size="100%">Bertrand, Daniel</style></author><author><style face="normal" font="default" size="100%">Leonard, Sherry</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.</style></title><secondary-title><style face="normal" font="default" size="100%">Biochem Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Biochem. Pharmacol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Allosteric Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">alpha7 Nicotinic Acetylcholine Receptor</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Bungarotoxins</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Cloning, Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Electrophysiological Phenomena</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Duplicate</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Linkage</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Isoxazoles</style></keyword><keyword><style  face="normal" font="default" size="100%">Ligands</style></keyword><keyword><style  face="normal" font="default" size="100%">Multigene Family</style></keyword><keyword><style  face="normal" font="default" size="100%">Oocytes</style></keyword><keyword><style  face="normal" font="default" size="100%">Patch-Clamp Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenylurea Compounds</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Binding</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Nicotinic</style></keyword><keyword><style  face="normal" font="default" size="100%">Reverse Transcriptase Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Schizophrenia</style></keyword><keyword><style  face="normal" font="default" size="100%">Smoking</style></keyword><keyword><style  face="normal" font="default" size="100%">Transfection</style></keyword><keyword><style  face="normal" font="default" size="100%">Xenopus laevis</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Oct 15</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">82</style></volume><pages><style face="normal" font="default" size="100%">904-14</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">&lt;p&gt;http://www.ncbi.nlm.nih.gov/pubmed/21718690?dopt=Abstract&lt;/p&gt;
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