@article {309768,
	title = {The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.},
	journal = {Biochem Pharmacol},
	volume = {82},
	year = {2011},
	month = {2011 Oct 15},
	pages = {904-14},
	abstract = {<p>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.</p>
},
	keywords = {Allosteric Regulation, alpha7 Nicotinic Acetylcholine Receptor, Animals, Bungarotoxins, Cell Line, Tumor, Cloning, Molecular, Electrophysiological Phenomena, Female, Genes, Duplicate, Genetic Linkage, Humans, Isoxazoles, Ligands, Multigene Family, Oocytes, Patch-Clamp Techniques, Phenylurea Compounds, Protein Binding, Receptors, Nicotinic, Reverse Transcriptase Polymerase Chain Reaction, RNA, Schizophrenia, Smoking, Transfection, Xenopus laevis},
	issn = {1873-2968},
	doi = {10.1016/j.bcp.2011.06.018},
	author = {Araud, Tanguy and Graw, Sharon and Berger, Ralph and Lee, Michael and Neveu, Estele and Bertrand, Daniel and Leonard, Sherry}
}
