This chapter suggests that contemporary scientific work with genetically engineered laboratory mammals has much in common with practices of domestication: it, too, deploys new technologies at the interface of lay and scientific cultures to collapse and reinscribe yet again Western cultural boundaries between humans and animals and between nature and nonnature. Recognizing the prominence of the domestication metaphor in genetics, past and present, calls to begin the difficult, but necessary, task of accounting for and intervening in the complicated process of technical, cultural, and political formation that its ongoing uses shape for humans and animals. Archaeological anthropologists describe such problems with the very idea of a “domestic animal.” Mouse fanciers routinized the activity of mouse breeding in captivity well before scientists became interested in this animal—and in so doing, established traditional husbandry assumptions while lowering the practical thresholds to mouse use in the laboratory.