Bedell, V.M. et al. Nature advance online publication (23 September 2012).

The lack of robust methods for targeted modification of the zebrafish genome has impeded many studies in this important vertebrate model organism. Engineered nucleases have been used to mutate the fish genome via the nonhomologous end-joining repair pathway, but genome editing by homology-directed repair (HDR) has so far proven elusive in this organism. Bedell et al. now demonstrate that transcription activator–like effector nucleases (TALENs) based on the GoldyTALEN scaffold are effective tools for editing the fish genome. They achieved biallelic mutations at several loci that recapitulate morpholino-generated loss-of-function phenotypes and that are transmitted through the germ line. In separate experiments, they used single-stranded oligonucleotides as donor templates for HDR-based introduction of sequences, including loxP sites, at targeted locations of the zebrafish genome.

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