Towards the cloning of genes underlying murine QTLs

Many quantitative trait loci (QTLs), including those for ethanol-related traits, have been mapped in the mouse. In light of rapidly developing tools and resources, we briefly review the strategy for identifying the genes underlying these QTLs. We note that positional cloning will soon be a matter of testing candidate genes rather than discovering genes; therefore, we describe a "congenic test'' to support that a candidate gene is indeed a QTL. Considering the rapid development of congenics and mutants, we also identify four areas of investigation-phenotypes, ethanol specificity, environment, and gene interactions-that might be exploited during the course of positional cloning to gain insights into QTL pathways. In particular, we note that multiple mutants of nearly every major neurotransmitter pathway have now been made. These mutants are not only useful for phenotypic tests, but also could be used to conduct "gene dependence" tests of QTLs. We also consider potential applications for the very recently developed ability to clone mice.