ZFIN ID: ZDB-PUB-091101-19
Nicotine response genetics in the zebrafish
Petzold, A.M., Balciunas, D., Sivasubbu, S., Clark, K.J., Bedell, V.M., Westcot, S.E., Myers, S.R., Moulder, G.L., Thomas, M.J., and Ekker, S.C.
Date: 2009
Source: Proceedings of the National Academy of Sciences of the United States of America   106(44): 18662-18667 (Journal)
Registered Authors: Balciunas, Darius, Clark, Karl, Ekker, Stephen C., Petzold, Andrew, Sivasubbu, Sridhar, Westcot, Stephanie
Keywords: behavior, addiction
MeSH Terms:
  • Animals
  • Behavior, Animal/drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Larva/drug effects
  • Larva/genetics
  • Mutagenesis, Insertional/drug effects
  • Mutation/genetics
  • Nicotine/pharmacology*
  • Zebrafish/genetics*
PubMed: 19858493 Full text @ Proc. Natl. Acad. Sci. USA
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.