Gene-targeting studies of mammalian behavior: Is it the mutation or the background genotype?

Gene targeting to create null mutations in mice is a powerful new tool in biology which will allow the molecular dissection of complex phenotypes such as mammalian brain function, and learning and memory. However, the attempt to interpret the phenotypical changes which arise in null-mutant mice is subject to several caveats. For example, the ability to disrupt a single gene in a targeted manner might lead one to overlook the effects of other genes. Ignoring the genetic background might lead to misinterpretation of results: the present article will demonstrate that the phenotypical abnormalities attributed to the null mutation in several molecular-neurobiological studies could simply result from the effects of background genes.