The Mammalian Functional Genomics Laboratory in Biosciences’ Environmental Genomics and Systems Biology (EGSB) Division has developed a higher-throughput transgenic mouse assay to evaluate the disease-causing potential of human variants in enhancers that turn on gene expression during development. The new approach leverages the CRISPR-Cas9 genome editing technology to create transgenic mice that carry an enhancer-reporter construct at a specific “safe harbor” location in the mouse genome. Because the transgenes are integrated in the same location in the genome there are no position effects, so fewer mice are needed to get reproducible results. To demonstrate proof of principle, the researchers used the new method—which they dubbed enSERT (enhancer inSERTion)—to examine nearly a thousand variants of one of the most well-characterized human enhancers that is associated with polydactyly (extra fingers or toes).