Mosaic eyes, genomic instability mutants, and cancer susceptibility

The zebrafish mosaic eye assay developed by George Streisinger (1984) takes advantage of the organism's transparency to provide an excellent assay for detecting somatic mutation. We now know that genomic instability contributes to cancer. We therefore took advantage of this assay to identify zebrafish mutants with increased frequencies of somatic mutation and spontaneous cancer. This chapter describes the details of mutagenesis and half-tetrad screening, the basis and practical use of the mosaic eye assay, and the histological methods used to study genomic instability mutants and cancer susceptibility. These techniques should prove useful to other zebrafish researchers, since they are broadly applicable to other biological investigations of zebrafish embryos, larvae and adults.