Studies using inbred mouse strains have already demonstrated the importance of heritable genetic factors in stress-response and stress-induced alterations in sleep pattern.14 Here we investigate a specific period gene, Per3, and evaluate how sequence variants in this gene alter transcription factor binding, gene expression and correlated behavior. In humans, variants in PER3 have been associated with differences in sleep homeostasis,15, 16 susceptibility and onset age of bipolar disorder, and different aspects of mood disorder including differences in novelty seeking.17, 18, 19, 20 In mice, expression of Per3 in the brain is highly variable in strains derived by crossing the B6 and D2 parental strains (the BXD family). We have exploited this normal endogenous variation in transcript abundance to explore the association between a circadian gene and complex stress and alcohol related behaviors.
