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REVIEWS
MICE, MICROBES AND MODELS OF INFECTION
Jan Buer* and Rudi Balling *
We urgently need animal models to study infectious disease. Mice are susceptible to a similar range of microbial infections as humans. Marked differences between inbred strains of mice in their response to pathogen infection can be exploited to analyse the genetic basis of infections. In addition, the genetic tools that are available in the laboratory mouse, and new techniques to monitor the expression of bacterial genes in vivo, make it the principal experimental animal model for studying mechanisms of infection and immunity.
Infectious diseases are more medically relevant than ever. More than a third of the annual worldwide deaths are the result of infectious diseases, such as malaria, tuberculosis and human immunodeficiency virus (HIV)/AIDS (see online link to the World Health Report 2002). There is an urgent need for animal models in the field of infectious diseases. In order to develop new therapies and vaccines, we need to have a detailed understanding of the events that are triggered in a host after bacterial, viral or parasitic infection. There is no substitute for using animal studies if we want to understand in detail the dynamics of hostpathogen interactions or the complex interactions between the different cell types and organs that are involved in the host response to a pathogen.
Mice are an ideal organism in which to understand human infectious diseases. Despite some differences, the immune systems of mice and humans are similar and they can often be challenged with the same, or similar, pathogens1. In this review, we argue that the mouse is an excellent model for the study of human infectious disease. To illustrate this, we focus specifically on bacterial infections and provide examples of studies using one of two genetic approaches that have been applied to the field of infectious disease: forward genetic screens and targeted gene knockouts. Forward genetic screens in mice have been used to identify and characterize genes that have a role in the susceptibility or resistance to infection. Targeted gene knockouts in mice have been used to characterize the mechanism of gene action during infectious
processes. In all cases, we emphasize how the tools that are available for the mouse geneticist can be used to...