In this MasterClass, the different steps that are requiered to generate a pertinent genetically engineered model will be detailed and explained. What is the purpose of a specific design? What does a conditional model mean? Is it better to fuse a reporter in N- or C-term of a protein? Should we use IRES (Internal Ribosome Entry Site) rather than 2A peptides when we need to coexpress two proteins under the same promoter. What sequences are required? The course will be largely illustrated with mouse and rat model examples and also cellular models. Case studies will illustrate the cours. A time for discussion and question will be left to participant. The advantages and inconveniences of using genome edition (focusing on CRISPR/Cas9 approaches) versus standard homologous recombination will largely be discussed.