The β3 subunit of the nicotinic acetylcholine receptor: Modulation of gene expression and nicotine consumption

Neuropharmacology
Helen M KamensMarissa A Ehringer

Abstract

Genetic factors explain approximately half of the variance in smoking behaviors, but the molecular mechanism by which genetic variation influences behavior is poorly understood. SNPs in the putative promoter region of CHRNB3, the gene that encodes the β3 subunit of the nicotinic acetylcholine receptor (nAChR), have been repeatedly associated with nicotine behaviors. In this work we sought to identify putative function of three SNPs in the promoter region of CHRNB3 on in vitro gene expression. Additionally, we used β3 null mutant mice as a model of reduced gene expression to assess the effects on nicotine behaviors. The effect of rs13277254, rs6474413, and rs4950 on reporter gene expression was examined using a luciferase reporter assay. A major and minor parent haplotype served as the background on which alleles at the three SNPs were flipped onto different backgrounds (e.g. minor allele on major haplotype background). Constructs were tested in three human cell lines: BE(2)-C, SH-SY5Y and HEK293T. In all cell types the major haplotype led to greater reporter gene expression compared to the minor haplotype, and results indicate that this effect is driven by rs6474413. Moreover, mice lacking the β3 subunit showed reduced voluntar...Continue Reading

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Citations

Jul 22, 2020·Autism Research : Official Journal of the International Society for Autism Research·Hafiz M MahmoodShakir D AlSharari
Aug 18, 2021·The European Journal of Neuroscience·Sean M Mooney-LeberHelen M Kamens

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