Using high-efficiency mouse germline mutagenesis to investigate complex biological phenomena: genetic diseases,...

A valuable approach to investigating a biological process is to study the effect of mutations in the involved genes. By studying a diverse set of such mutations, one can gain important insights into the roles that the given gene product plays in the biological process. Although this approach has long been recognized, the scarcity of mammalian mutations has largely limited such investigations to simple organisms. It has recently been shown that highly efficient mutagenesis of the mouse germline with a random point mutagen can produce mutations that are valuable in several important ways. First, it can produce numerous different types of mutations. Second, it can be used to mutate genes that have yet to be cloned or characterized. Genes that have been marked by mutation can ultimately yield molecular access after mapping to high resolution and cloning from map position. Such new investigative capabilities will ultimately allow one to gain intimate knowledge of the molecular basis of complex biological processes like behavior and development. Third, mutations can be induced that yield animal models of human heritable diseases. Such disease models allow for intensive research into the etiology of the given disease and also permit the facile evaluation of new therapeutic regimens.