The use of gene knockout mice in thermoregulation studies

As the use of gene knockout models in thermoregulation studies has gained popularity, the reported incidence of redundant or discrepant phenotypes between studies has also increased. Several gene knockout models mimic human processes and have provided valuable insight into the role of endogenous mediators in thermoregulatory processes. There are also many examples of mutant strains expressing virtually identical phenotypes as their wild-type controls, causing concern regarding the appropriateness of these models for the study of physiological processes. In some cases, discrepancies in results are being reported from different laboratories that are studying the same gene knockout model. While mutant strains provide a powerful tool for analysis of gene function in vivo, the breeding strategies used to generate the strain may have a profound impact on the expressed phenotype. This review examines the intricacies of working with a small rodent such as the mouse and discusses the advantages and disadvantages of using gene knockout models for thermoregulatory research. A number of experimental strategies that can be used to minimize the occurrence of redundant phenotypes are presented. The influence of background strain effects is also considered, since this may be one of the most important factors influencing a mutant phenotype. A future perspective is provided in which more advanced technologies using conditional gene inactivation and the production of rat knockout strains will improve current experimental design.