Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.

Department of Laboratory Medicine and Pathology Institute for Translational Neuroscience University of Minnesota Minneapolis MN 55455 USA

Department of Neurology and German Center for Vertigo and Balance Disorders Hospital of the Ludwig Maximilians University Munich Campus Grosshadern Marchioninistr 15 81377 Munich Germany

Department of Neurology University of Utah 175 North Medical Drive East Salt Lake City UT 84132 USA

Department of Neurophysiology and Neural Repair Gunma University Graduate School of Medicine 3 39 22 Gunma 371 8511 Japan

Department of Neuroscience Institute for Translational Neuroscience University of Minnesota Minneapolis MN 55455 USA

Department of Pathophysiology Faculty of Medicine in Pilsen Charles University alej Svobody 75 323 00 Plzen Czech Republic

Laboratory of Neurodegenerative Disorders Biomedical Center Faculty of Medicine in Pilsen Charles University alej Svobody 75 323 00 Plzen Czech Republic

Service des Neurosciences Université de Mons UMons Mons Belgium

The Department of Cellular and Integrative Physiology University of Texas Health Science Center at San Antonio 7703 Floyd Curl Drive MC 7843 San Antonio TX 78229 USA

Unité des Ataxies Cérébelleuses Service de Neurologie CHU Charleroi Charleroi Belgium

Viral Vector Core Gunma University Initiative for Advanced Research Gunma 371 8511 Japan

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Lurcher Mouse as a Model of Cerebellar Syndromes

Reduction of Microvessel Number and Length in the Cerebellum of Purkinje Cell Degeneration Mice

Experimental Treatment with Edaravone in a Mouse Model of Spinocerebellar Ataxia 1