Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour

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dc.contributor.author Garcia-Gonzalez, Judit
dc.contributor.author Brock, Alistair J.
dc.contributor.author Parker, Matthew O.
dc.contributor.author Riley, Riva J.
dc.contributor.author Joliffe, David
dc.contributor.author Sudwarts, Ari
dc.contributor.author Teh, Muy-Teck
dc.contributor.author Busch-Nentwich, Elisabeth M.
dc.contributor.author Stemple, Derek L.
dc.contributor.author Martineau, Adrian R.
dc.contributor.author Kaprio, Jaakko
dc.contributor.author Palviainen, Teemu
dc.contributor.author Kuan, Valerie
dc.contributor.author Walton, Robert T.
dc.contributor.author Brennan, Caroline H.
dc.date.accessioned 2020-04-14T09:07:01Z
dc.date.available 2020-04-14T09:07:01Z
dc.date.issued 2020-03-25
dc.identifier.citation Garcia-Gonzalez , J , Brock , A J , Parker , M O , Riley , R J , Joliffe , D , Sudwarts , A , Teh , M-T , Busch-Nentwich , E M , Stemple , D L , Martineau , A R , Kaprio , J , Palviainen , T , Kuan , V , Walton , R T & Brennan , C H 2020 , ' Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour ' , eLife , vol. 9 , 51295 . https://doi.org/10.7554/eLife.51295
dc.identifier.other PURE: 135351114
dc.identifier.other PURE UUID: 934e5b9d-0a32-47bc-a14c-b42fe9ffa4e6
dc.identifier.other WOS: 000522154300001
dc.identifier.other ORCID: /0000-0002-7847-8384/work/72306069
dc.identifier.uri http://hdl.handle.net/10138/313975
dc.description.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-3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F-0 fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F-3 fish, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of slit3 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 htr1aa 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. en
dc.format.extent 33
dc.language.iso eng
dc.relation.ispartof eLife
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject CONDITIONED PLACE PREFERENCE
dc.subject 5-HT1A RECEPTOR
dc.subject GENE-EXPRESSION
dc.subject ACOUSTIC STARTLE
dc.subject DANIO-RERIO
dc.subject VITAMIN-D-3 SUPPLEMENTATION
dc.subject SPATIOTEMPORAL EXPRESSION
dc.subject PREPULSE INHIBITION
dc.subject DOPAMINE D-1
dc.subject MICE LACKING
dc.subject 3111 Biomedicine
dc.title Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Department of Public Health
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization Genetic Epidemiology
dc.contributor.organization HUS Helsinki and Uusimaa Hospital District
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.7554/eLife.51295
dc.relation.issn 2050-084X
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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