A CONSIDERATION OF THE ADVANTAGES AND POTENTIAL DIFFICULTIES OF THE USE OF TRANSGENIC MICE FOR THE STUDY OF GERMINAL MUTATIONS

The utility of transgenic mouse systems in the study of germ-cell mutations is discussed. These systems promise to fill a gap in the evaluation of potential genotoxic agents between the identification of mutagens in short-term test systems and evaluation of human genetic risk. A less appreciated major contribution that transgenic systems can make is as research tools for achieving an understanding of the mechanisms of mutation induction in germ cells. Questions concerning the germ-cell mutations using transgenic systems include whether these systems can detect large genetic lesions, whether they can detect mutations in repair-deficient male germ-cell stages, whether it is valid to extrapolate mutational spectra from transgenes to endogenous genes, and whether the transgenic systems can be used to address issues concerning differences in locus sensitivities to mutation. Available shuttle-vector systems are not suitable for the direct detection of mutations in female germ cells. Future directions for development include the use of the present systems in research and testing and the development of systems with new capabilities.