In this study, we used an integrative approach to relate gene expression variation of Per3 with systems level phenotypes. We found that a local sequence variant contributes to significant differences in the mRNA and protein level of Per3 among the BXD family as well as the parental B6 and D2 strains. Such quantitative differences in mRNA were correlated with physiological and behavioral traits related to stress and addiction, suggesting that natural variations in Per3 may be causally associated with these traits. Treatments with alcohol and acute restraint in turn had significant effects on Per3 expression. The combined analysis of downstream genes and differential expression between KO and wildtype showed that Per3 has functional implications in alcohol and stress response.
