Influence of genetic background on alcohol drinking and behavioral phenotypes of 5-HT3 receptor over-expressing mice

Behavioral effects of genetic manipulations are influenced by the background genetics of mouse strains used for the creation of transgenic mice. One strategy to address whether background genes may compromise interpretation of phenotype is the production of congenics. 5-HT3 receptor over-expressing mice have been behaviorally characterized on a B6SJL/F2 background (B6SJL/F2-OE mice), and were found to consume less ethanol failed to develop conditioned place preference to moderate doses of cocaine and demonstrate improved hippocampal-dependent learning. To assess the contribution of parental strain genetics to these behaviors, we bred the transgene onto two well-defined backgrounds that differ in ethanol consumption and contextual fear conditioning, C57Bl/6J (B6) and DBA/2J (D2) strains. The behavioral phenotype of B6SJL/F2-OE was recapitulated in C57Bl/6J-OE mice. However, the effect of transgene over-expression on behavior was only apparent for one aspect of the novelty test using DBA/2J-OE mice. Results underscore the need to consider the genetic environment conferred by strain selection on the effects of genetic manipulation in mice.