Experimental models of dystonia

Abstract

Dystonia is a disabling movement disorder characterized by involuntary, sustained muscle contractions, with repetitive twisting movements and abnormal postures. It is clinically classified as primary, either sporadic or genetic, or secondary, following focal brain lesions. The recent past has witnessed remarkable progress in finding genes for dystonia. However, translating the findings from genetics into concrete changes for dystonic patients is not immediate, as it requires extensive exploration of the consequences of gene defects on motor behavior, protein biochemistry, and cell physiology. Thus, in the last decade, a number of animal models have been generated and, to some extent, characterized. These include distinct species, ranging from invertebrates, such as Caenorhabditis elegans and Drosophila melanogaster, to rodents and nonhuman primates. The mouse is the average choice of mammalian models in most laboratories, particularly when manipulations of the genome are planned. Investigations of animals provide results that do not always reproduce the clinical features of human dystonia. Indeed, most of the mouse models of inherited dystonia do not exhibit overt dystonia although they do have subtle motor abnormalities and well-characterized neurochemical and neurophysiological alterations. Conversely, spontaneous mutant models display a clear phenotype, but in some cases the origin of the mutation is unknown. In spite of such limitations and apparent contradictory evidence, there is general consensus on the notion that a useful animal model has to be judged by how reliably and effectively it can be used to explore novel aspects of pathophysiology and potential treatments. In the present work, we briefly describe the most commonly utilized models for the study of dystonia and the results obtained, in attempt to provide a comprehensive overview of the current, available models.