The chapter discusses the methods and outcomes of germ-line transformation in mice, focusing on the introduction of functional genes into the genome. Key techniques include pronuclear microinjection, which has been widely used to introduce cloned DNA into fertilized eggs, and other methods such as retroviral infection and the use of totipotent teratocarcinoma cells. The integration of foreign DNA into the genome can result in stable transmission for many generations, though mosaicism and rearrangements can occur. The chapter also explores the expression of introduced genes, including tissue-specific and developmental regulation, as well as the physiological consequences of transgene expression, such as growth control and cancer induction. Examples of successful and unsuccessful transgene expression are provided, highlighting the complex interactions between regulatory elements and chromosomal context. The chapter concludes by discussing the potential applications and challenges of germ-line transformation in mammalian genetics.The chapter discusses the methods and outcomes of germ-line transformation in mice, focusing on the introduction of functional genes into the genome. Key techniques include pronuclear microinjection, which has been widely used to introduce cloned DNA into fertilized eggs, and other methods such as retroviral infection and the use of totipotent teratocarcinoma cells. The integration of foreign DNA into the genome can result in stable transmission for many generations, though mosaicism and rearrangements can occur. The chapter also explores the expression of introduced genes, including tissue-specific and developmental regulation, as well as the physiological consequences of transgene expression, such as growth control and cancer induction. Examples of successful and unsuccessful transgene expression are provided, highlighting the complex interactions between regulatory elements and chromosomal context. The chapter concludes by discussing the potential applications and challenges of germ-line transformation in mammalian genetics.