Identification of therapeutic drug targets through genetically manipulated mice: Are we getting it right?

A significant contribution to the identification of therapeutic targets in disease control and management has been made through the use of genetically modified mice in which specific gene function was altered. However, the genetic background of these mice can have a strong influence on the observed phenotype and, if not properly controlled, can lead to misinterpretation of data and incorrect conclusions as to the importance of particular genes in disease states. Nevertheless, it is becoming apparent that advantages may also ensue, since analysis of gene function in mixed (or a number of different) genetic backgrounds may more closely approximate the human genome and provide the potential to identify modifier genes and polymorphisms which influence the resulting phenotype of the target gene. A rigorous analysis of these strain-specific modifications of molecular function may thus afford a deeper understanding of the mechanisms underlying gene function and permit the development of more selective, specific and subtle molecular therapeutic approaches.