Insight into the physiological actions of thyroid hormone receptors from genetically modified mice

Abstract

Analysis of the literature indicates that understanding the mechanism of T3 action in vivo has been advanced significantly by the generation of transgenic and knockout mice involving the TRα and β genes. These mice have provided detailed insight into the roles of the various TR isoforms. However, it is prudent to interpret data obtained from genetically modified mice with caution because of the unavoidable compensatory biological responses that occur following gene deletion or over-expression. Such responses may reveal phenotypes that are indirectly related to TR function or may mask important direct actions of TRs that can be performed by other, normally redundant, pathways. Furthermore, whilst comparisons between genetically modified mice can be very informative, an additional drawback is that different laboratories engineer mutations in mice with different genetic backgrounds. Such differences may result in significant phenotypic modification. In future studies, therefore, it will be helpful to compare mutations of the TRα and β genes on uniform genetic backgrounds. In spite of these caveats, genetically modified mice have enabled T3-signalling pathways to be dissected in the intact animal. They have revealed the enormous complexity of TR function and provided a new and deeper understanding of the physiological actions of thyroid hormones.