Factors that affect the molecular nature of germ-line mutations recovered in the mouse specific-locus test

The morphological specific locus test (SLT), which allows the scoring of 2,000 loci/hr/person, has been in use for four decades for measuring mammalian germ-line mutation rates under various conditions of exposure. More recently, the SLT's capabilities for the qualitative characterization of mutations have been exploited. The large sets of mutations centered on specific loci that have been accumulated over the years, including sets of nested deletions, have provided prime material for fine-structure genetic analyses. Subsequent molecular entry to these regions has led to intensive physical/functional mapping of megabase segments of the genome. In turn, these investigations have generated genetic and molecular tools for analyzing individual mutations as to extent and nature of the genomic lesion. Using the results of such analyses, it has been shown that germ-cell-stage at which mutagenic treatment is administered, rather than the nature of the mutagen used, may be the chief determinant of the nature of genomic lesions. These and related quantitative findings now make it possible to optimize conditions for the use of mutagens in providing desired types of mutations as tools (e.g., high incidences of deletions or other rearrangements vs. high incidences of point mutations).