Nicotine response genetics in the zebrafish.
Tobacco use is predicted to result in over 1 billion deaths worldwide by the end of the 21(st) century. How genetic variation contributes to the observed differential predisposition in the human population to drug dependence is unknown. The zebrafish (Danio rerio) is an emerging vertebrate model system for understanding the genetics of behavior. We developed a nicotine behavioral assay in zebrafish and applied it in a forward genetic screen using gene-breaking transposon mutagenesis. We used this method to molecularly characterize bdav/cct8 and hbog/gabbr1.2 as mutations with altered nicotine response. Each have a single human ortholog, identifying two points for potential scientific, diagnostic, and drug development for nicotine biology and cessation therapeutics. We show this insertional method generates mutant alleles that are reversible through Cre-mediated recombination, representing a conditional mutation system for the zebrafish. The combination of this reporter-tagged insertional mutagen approach and zebrafish provides a powerful platform for a rich array of questions amenable to genetic-based scientific inquiry, including the basis of behavior, epigenetics, plasticity, stress, memory, and learning.
University of Minnesota, Minneapolis, MN 55455, USA.
Andrew M
AM
Petzold
Darius
D
Balciunas
Sridhar
S
Sivasubbu
Karl J
KJ
Clark
Victoria M
VM
Bedell
Stephanie E
SE
Westcot
Shelly R
SR
Myers
Gary L
GL
Moulder
Mark J
MJ
Thomas
Stephen C
SC
Ekker
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007814:Larva / Q000187:drug effects / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology*; D015027:Zebrafish / Q000235:genetics*
D009538:Nicotine