Role of mouse germ-cell mutagenesis in understanding genetic risk and in generating mutations that are prime tools for studies in modern biology

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Abstract
Highlights are presented on (1) the role mouse germ‐cell mutagenesis has played in assessing the genetic harm from radiations and chemicals, and (2) the contributions to the field of modern biology that are being made by the products of this research—the propagated mutations. Among the numerous findings in radiation mutagenesis were the humped dose‐effect curve for spermatogonial stem cells, the major differences between the sexes and between germ‐cell stages of each sex in both yield and nature of mutations, the dose‐rate effect, which provided the first evidence for repair of mutational (or premutational) damage, the augmenting effect of certain regimes of dose fractionation, and many others. Chemical mutagenesis studies that followed revealed at least three patterns of mutation yield and demonstrated that germ‐cell stage—much more than the nature of the chemical—governs the nature of the DNA lesions induced. Two “supermutagens,” one for intragenic mutations and one for deletions and other rearrangements, have become very useful in the manufacture of mutations for specific purposes. The mutations propagated from radiation‐and chemical‐mutagenesis experiments are providing prime resources for basic studies in genome organization, gene structure, and function. DNA lesions that involve specific loci have made possible increasingly detailed characterization of extensive deletion complexes that facilitate high‐intensity physical and functional mapping within them. Numerous loci associated with interesting developmental anomalies have been identified and have become accessible to positional cloning. Several of the genes accessed with the aid of induced mutations (deletions, other rearrangements, and point mutations) are furnishing prime reagents for elucidating human disease conditions.

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