Mutational inactivation of a specific gene is the most powerful technique to analyze the biological function of the gene. This approach has been used for a long time in viruses, bacteria, yeast, and fruit fly, but looked quite hopeless in more complex organisms. Targeted inactivation of specific genes (also known as knock-out mutation) in mice is arguably one of the most significant achievements in modern biology. The test presented in this article describes the procedure developed in the laboratory of one of the Nobel laureates of 2007, Mario Capecchi. Terms to be familiar with before one starts to solve the test: mutation, vector, plasmid, origin of replication, promoter, introns/exons, open reading frame, transfection, circular and linear DNA, DNA integration, homologous recombination, DNA replication, gene expression, heterozygote, and homozygote. (Contains 2 figures.)