Towards the cloning of genes underlying murine QTLs

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