Over the last 40 years, genetically engineered mouse models (GEMMs) have facilitated tremendous progress in mammalian biology, leading to a comprehensive understanding of the genetic regulation of normal and disease development and, in some cases, life-saving diagnoses and therapies. Bin Gu has spearheaded critical technological advancements and tool development in mouse genetics, including efficiently modifying mouse genome (Nature Biotechnology 2018), visualizing signaling dynamics (Open Biology 2022), and precise gene manipulation (eLife 2022). Building on this expertise, we strive to develop and integrate cutting-edge mouse genetic tools for solving biomedical problems currently lacking appropriate models.