Generating mouse models that have targeted genetic mutations currently relies on the use of targeting vectors and mutant embryonic stem cells (ESCs). Wefers et al. identified a new, quicker way of making mouse models of disease by microinjecting transcription activator-like effector nucleases (TALENs) and synthetic oligodeoxynucleotides into single-cell embryos. The authors created disease-relevant, correctable mutations in the small GTPase RAB38. This technology enabled heterozygous mutant mice to be available within 18 weeks (ESC-based mutant mice can take a year or longer to produce).