Genomic Knockout of Two Presumed Forelimb Tbx5 Enhancers Reveals They Are Nonessential for Limb Development (Cell Reports)

Forelimb development requires Tbx5. Using CRISPR/Cas9 gene editing to create homozygous deletions, Cunningham et al. show that two Tbx5 forelimb enhancers identified with reporter transgenes are not required for Tbx5 activation or forelimb development. These observations demonstrate that knockout studies are required to identify endogenous enhancers necessary for biological processes.