[Frontiers in Bioscience 13, 3775-3785, May 1, 2008]

Being a mouse in a man's world: what TMEV has taught us about human disease

Kristen M. Drescher, Danuta Sosnowska

Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178

TABLE OF CONTENTS

1. Abstract
2. An overview of the Theiler's model of demyelinating disease
3. Multiple Sclerosis - the short course
4. Axonal injury in demyelinating disease. Does demyelination really matter?
4.1. Axonal injury in multiple sclerosis
4.2. What has Theiler's virus taught us about demyelination and axonal injury?
4.3. Mechanism of axonal injury in the TMEV model
5. Lessons from the acute phase of TMEV infection
6. Peripheral nervous system infection
7. Summary and Perspectives
8. Acknowledgements
9. References

1. ABSTRACT

Choosing an appropriate animal model to study a disease is guided by a variety of factors including but not limited to the questions being asked, availability of reagents, knowledge of the animal species, personal biases of the researcher, and in some cases, cost and availability of facilities to effectively investigate the model. The validity of an animal model can be further complicated when the etiology of the disease is incompletely defined. Examples of these diseases include multiple sclerosis (MS) and type 1 diabetes (T1D). In addition to host genetics, epidemiological studies have implicated infectious agents, in particular viruses as triggers of these diseases. Thus many studies of these diseases have focused on modeling the interactions of viruses and the host immune response in vivo in small animals. Theiler's murine encephalomyelitis virus (TMEV) infection of mice has been used for over 30 years as a model of virus-induced demyelination. TMEV induces a MS-like disease in susceptible strains of mice but does not cause pathology in humans. While some researchers may question the rationale for using a non-human pathogen to model human disease, the TMEV model of central nervous system (CNS) demyelination has permitted study of some aspects of human MS which would have been difficult to address in other models of the disease. Despite being 'merely a disease of mice,' many of the findings in the Theiler's virus model are directly applicable to the human condition, and studies from the model are responsible for our current understanding of mechanisms of pathology and clinical disability in human MS. In this review we will present some of the key findings from the TMEV model in the context of human disease.