A new approach to the study of chemically-induced germ-line mutations using transgenic fish

A new approach using transgenic fish to quantify mutations directly in a genomically integrated mutation target gene has shown significant promise for improved analyses of germ-line mutations. Transgenic medaka carrying the cII target gene were exposed to the potent germ cell mutagen, ethylnitrosourea (ENU), and bred for 6 days before and after exposure to untreated non-transgenic females. Offspring carrying mutated cII genes were readily identified using the cII mutation detection assay. Mutant frequencies in the cII target gene of offspring from exposed males were elevated significantly above those from the same males before exposure, and the highest mutant frequency observed was 2.62 X 10 ^-2 . Sequencing offspring with elevated mutant frequencies revealed identical mutations in all or multiple cells. Transgenic mutation assays are a powerful approach for detecting mutations in vivo, and this approach could make germ-line mutagenesis studies more efficient and economical.