The greatest success story for alcohol-related QTL mapping in rodents has been the discovery of a quantitative trait gene (QTG)9 that affects acute withdrawal severity from both alcohol and pentobarbital in mice. Originally, investigators mapped several QTLs contributing to this trait to locations on various mouse chromosomes (Buck et al. 1997). Subsequent studies with a variety of specifically created genetic animal models gradually narrowed down the size of the DNA region (i.e., reduced the confidence interval) around one of these QTLs until only a few genes remained within the confidence interval. Functional studies then demonstrated that the most likely gene contributing to the trait was Mpdz, which encodes a protein containing multiple structural components known as PDZ-domains (Shirley et al. 2004). Studies of this gene’s pattern of expression in the brain and of the functions of the MPDZ protein continue, as do studies to identify the receptor molecules with which MPDZ interacts (e.g., the serotonin 2C receptor) (Chen et al. 2008a; Reilly et al. 2008).
