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

Show full item record



Permalink

http://hdl.handle.net/10138/313975

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

Title: Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour
Author: Garcia-Gonzalez, Judit; Brock, Alistair J.; Parker, Matthew O.; Riley, Riva J.; Joliffe, David; Sudwarts, Ari; Teh, Muy-Teck; Busch-Nentwich, Elisabeth M.; Stemple, Derek L.; Martineau, Adrian R.; Kaprio, Jaakko; Palviainen, Teemu; Kuan, Valerie; Walton, Robert T.; Brennan, Caroline H.
Contributor organization: Institute for Molecular Medicine Finland
Department of Public Health
Helsinki Institute of Life Science HiLIFE
Faculty of Medicine
University of Helsinki
Genetic Epidemiology
HUS Helsinki and Uusimaa Hospital District
Date: 2020-03-25
Language: eng
Number of pages: 33
Belongs to series: eLife
ISSN: 2050-084X
DOI: https://doi.org/10.7554/eLife.51295
URI: http://hdl.handle.net/10138/313975
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.
Subject: CONDITIONED PLACE PREFERENCE
5-HT1A RECEPTOR
GENE-EXPRESSION
ACOUSTIC STARTLE
DANIO-RERIO
VITAMIN-D-3 SUPPLEMENTATION
SPATIOTEMPORAL EXPRESSION
PREPULSE INHIBITION
DOPAMINE D-1
MICE LACKING
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
elife_51295_v1.pdf 3.177Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record