Manipulating gene expression is a commonly used tool to study the effect of a single gene or the hierarchy of gene networks in many different biological disciplines. When working with mice, the most commonly used techniques to manipulate genes include gene targeting via homologous recombination to achieve loss-of-function and gain-of-function mutations. Students often struggle with the concepts behind homologous recombination and the physical changes that happen at the target gene locus. Our activity uses different colored ribbons connected by hook-and-loop fasteners (e.g., those most popularly produced by the VELCRO Brand) that students use to design targeting constructs as well as to model the recombination between their constructs and the gene locus. This hands-on exercise helps students better understand the mechanisms of homologous recombination happening at the gene locus, enabling them to progress to higher-level cognition such as predicting experimental outcomes and designing their own gene targeting experiments.