Clinical relevance of humanized mice

Abstract

Mice have been used in basic science research over decades as small in vivo models to study human immunity and disease. Despite their shortcomings, they have yielded valuable information that lead to the development of effective therapies against cancer and other infectious diseases. However, the appearance of HIV in the 1980s posed a major challenge; the virus only targeted human CD4 T cells, thus rendering mouse models not useful to study the disease. In the late 1980s, researchers at various institutions began developing chimeric mouse models. Immunodeficient mice were transplanted with human immune cells or hematopoietic tissues that gave rise to chimeric mice that carried a somewhat functional human immune system. These early chimeric animals proved quite valuable in the study of HIV pathogenesis and latency. However, the lack of peripheral reconstitution limited the scope of many studies. During the past few years, more advanced models have been developed. The new chimeric animals have been peripherally reconstituted with most if not all lineage cells of the human immune system. As such, humanized mice were no longer used only for HIV but also for other diseases including cancer. Here, we will discuss the older and newer systems and examine their relevance in the development of new and effective therapies against disease.