Transgenic Animal Models

Abstract

Exercise adaptations induce the differential expression of genes that encode components of the contractile apparatus, metabolic pathways, organelle systems, and membrane components. These changes in gene expression are presumably brought about by the activation of intracellular signaling pathways. The use of transgenic technology is particularly well suited for exercise studies because it uniquely allows investigators to evaluate gene regulatory mechanisms in the intact animal at all stages of the life cycle. Transgenic mice can be generated that harbor any of the varied genes involved in exercise adaptation, for the purpose of determining what sequences within this gene regulate the response to any exercise regimen. Once the corresponding transcriptional factor(s) have been identified and the gene(s) cloned, a series of similar studies (gene networking) could be undertaken to determine the signal transduction pathway. Alternatively, transgenics can be produced that overexpress a particular protein or express an isoform of a protein in a tissue where it is not normally expressed. The goal of these studies would be to determine if function is improved and if exercise adaptation is enhanced or facilitated. Ultimately, gene targeting can be used to either mutate or knock out a gene to determine whether its gene product is indispensable for function, exercise performance, and/or adaptation.