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Identification of as a locus affecting nicotine preference in zebrafish and human smoking behaviour. | LitMetric

AI Article Synopsis

Article Abstract

To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F fish, one in the gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096180PMC
http://dx.doi.org/10.7554/eLife.51295DOI Listing

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