Application of exogenously regulatable promoter systems to transgenic models for the study of aging

Abstract

Transgenic mouse and gene knockout technologies offer powerful tools for dissecting the roles of specific genes in the process of aging. The interpretation of the results of such studies is limited, however, by the fact that the gene of interest is over- or underexpressed throughout the life span of the animal model. Among other problems, this situation makes it difficult to separate the effects that a specific gene has on embryological development from those that it may exert on the subsequent maturation and aging of the animal. It is also not possible with these methods alone to alter the expression of genes in an age-dependent fashion and to assess the effects of these alterations on the aging process. This capacity would be of particular interest in studying genes which are thought to have a role in regulating physiological homeostasis. Because they offer the opportunity to activate or render inactive the expression of genes at will, exogenously regulatable promoter systems, particularly when used in combination with traditional transgenic or gene knockout approaches, provide a new and potentially very powerful tool for studying the effect of selected genes on aging. This review discusses the merits and limitations of the application of either the tetracycline-regulatable promoter system, the RU486-inducible promoter system, or the ecdysone-inducible promoter system to exogenously regulate the expression of a transcriptionally linked gene and to thus assess the effect of that gene on aging.