Arguably, the main challenge for contemporary genetics is to understand the function of every gene in a mammalian genome. The mouse has emerged as a model for this task because its genome can be manipulated in a number of ways to study gene function or mimic disease states. Two complementary genetic approaches can be used to generate mouse models. A reverse genetics or gene-driven approach (gene to phenotype) starts from a known gene and manipulates the genome to create genetically modified mice, such as knockouts. Alternatively, a forward genetics or phenotype-driven approach (phenotype to gene) involves screening mice for mutant phenotypes without previous knowledge of the genetic basis of the mutation. N-ethyl-N-nitrosourea (ENU) mutagenesis has been widely used for both approaches to generate mouse mutants. Here we review progress in ENU mutagenesis screening, with an emphasis on creating mouse models for human disorders.

Unstable linkage between genetic markers in transformation. J. Bacteriol. 89:1314-1321. 1965.-A new type of association of genetic markers in a transformation system has been discovered. Linkage between certain markers is detectable only under particular conditions of deoxyribonucleic acid (DNA) extraction and is sensitive to dilution of the DNA. The data suggest that this unstable association occurs between markers which are on the same molecule but separated by a molecular distance sufficiently great for linkage to be preserved only by mild DNA extraction procedures and at high concentrations of DNA. Linkage can be stabilized by dilution in the presence of a carrier DNA. By use of these unstable linkages, the genetic map of Bacillus subtilis has been extended in both directions from the aromatic gene cluster.

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