Viewpoint: Are studies in genetically altered mice out of control?

Because the use of transgenic and gene-targeted models has increased in pop ularity, the number of reports describing unpredictable phenotypic effects caused by variation in the genetic background used to generate or propagate these models has steadily increased. There are now many examples in which animals containing the same exact genetic manipulation exhibit profoundly d ifferent phenotypes when present on diverse genetic backgrounds, demonstrat ing that genes unrelated, per se, to the ones being targeted can play a sig nificant role in the observed phenotype. Herein, I will discuss (1) the sou rce of genetic variability in mutant mouse models, (2) the appropriateness of using inbred mice as controls, and (3) strategies to help minimize genet ic variation between experimental and control mice.