Interpretation of phenotype in genetically engineered mice

Background and Purpose: In mice, genetic: engineering involves two general approaches-addition of an exogenous gene, resulting in transgenic mice, and use of knockout mice, which have a targeted mutation of an endogenous gene . The advantages of these approaches is that questions can be asked about t he function of a particular gene in a living mammalian organism, taking int o account interactions among cells, tissues, and organs under normal, disea se, injury, and stress situations. Methods: Review of the literature concentrating principally on knockout mic e and questions of unexpected phenotypes, lack of phenotype, redundancy and effect of genetic background on phenotype will be discussed. Conclusion: There is little gene redundancy in mammals; knockout phenotypes exist even if none are immediately apparent; and investigating phenotypes in colonies of mixed genetic background may reveal not only more phenotypes , but also may lead to better understanding of the molecular or cellular me chanism underlying the phenotype and to discovery of modifier gene(s).