Dystonia: Are animal models relevant in therapeutics?

Abstract Dystonia refers to a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions leading to repetitive twisting movements and abnormal postures. A better understanding of the etiology, pathogenesis and molecular mechanisms underlying dystonia may be obtained from animal models. Indeed, while studies in vitro using cell and tissue models are helpful for investigating molecular pathways, animal models remain essential for studying the pathogenesis of these disorders and exploring new potential treatment strategies. To date, the mouse is the most common choice for mammalian models in most laboratories, particularly when manipulations of the genome are planned. Dystonia animal models can be classified into two categories, etiological and symptomatic, although neither is able to recapitulate all features of these disorders in humans. Nevertheless, etiological and symptomatic animal models have advantages and limitations that should be taken into consideration according to the specific proposed hypothesis and experimental goals. Etiological mouse models of inherited dystonia can reproduce the etiology of the disorder and help to reveal biochemical and cellular alterations, although a large majority of them lack motor symptoms. Conversely, symptomatic models can partially mimic the phenotype of human dystonia and test novel pharmacological agents, and also identify the anatomical and physiological processes involved, although the etiology remains unknown. Thus, our brief survey aims to review the state of the art as regards most of the commonly used animal models available for dystonia research.