ABSTRACT

Since the development, in the 1980s, of routine procedures for gene addition or modification to generate transgenic animals, principally mice, it may be estimated that several thousands of transgenic lines have been produced worldwide. The key to both rederivation techniques is the ability to maintain, without pathogen spread, contaminated colonies in close vicinity of pathogen-free colonies of foster or surrogate mothers. This entails an absolute physical separation between the contaminated and clean colonies, notably including use of separate personnel for routine maintenance of the two colonies. The phenotypic expression of a transgenic modification, either by gene addition or replacement, clearly depends on the extent to which the genetic background can compensate for change introduced by the experimenter. Indeed, genetic standardization comprises rapid generation turn-over, thus increasing the risk of transgene re-arrangement or change in expression levels. Although transgene loss or rearrangement is thought to be rare, there have been instances where transgene expression levels are progressively lost over successive generations.