Gene targeting: applications in transplantation research.
Gene targeting, the manipulation of gene in the mouse genome using homologous recombination in embryonic stem cells, is a powerful experimental tool that has been widely utilized in a number of disciplines. The ability to precisely alter genes in this way provides an avenue for investigating the role of a gene product in normal and pathological processes in the intact animal, with a precision and efficacy not possible using pharmacological agents, antibodies or engineered proteins. In transplant research, gene targeting provides a unique tool for discriminating the contributions of gene expression in donor versus recipient tissues. This review focuses on several areas in transplantation research where gene targeting has made useful contributions. These include studies of the role of donor and recipient multiple histocompatibility complex antigens in regulating rejection responses, the role of CD4+ T cell in mediating acute rejection, and the functions of cytokines during rejection and tolerance induction. These studies highlight the unique advantages of gene targeting in studies of complex processes in whole animals and illustrate the contributions of this technique to understanding the pathogenesis of allograft rejection.
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