Abstract
Spinocerebellar ataxia type 1 (SCA1) is one of a group of dominantly inherited neurodegenerative diseases caused by a mutant expansion of a polyglutamine-repeated sequence within the affected gene. One of the major cell types affected by the gene (ataxin-1) mutation in SCA1 is the cerebellar Purkinje cell. Targeted expression of mutant ataxin-1 in Purkinje cells of transgenic mice produces an ataxic phenotype with pathological similarities to the human disease. Other transgenic experiments using altered forms of mutant ataxin-1 have shown that nuclear localization of the mutant protein is necessary for pathogenesis and that nuclear aggregates of ubiquitinated mutant protein, while a feature of SCA1 and other polyglutamine diseases, are not a requirement for pathogenesis in transgenic models of SCA1. Present and future generations of transgenic mouse models of SCA1 will be valuable tools to further address mechanisms of pathogenesis in polyglutamine-related disorders.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Ataxin-1
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Ataxins
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Brain / pathology
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Cell Nucleus / metabolism
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Cell Nucleus / pathology
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Cell Nucleus / ultrastructure
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Cerebellum / pathology
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Cerebellum / ultrastructure
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Cranial Nerves / pathology
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Disease Models, Animal*
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Humans
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Mice
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Mice, Transgenic
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Neurodegenerative Diseases / genetics
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / pathology*
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Olivopontocerebellar Atrophies / pathology
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Peptides / genetics*
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Purkinje Cells / pathology
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Purkinje Cells / ultrastructure
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Spinal Cord / pathology
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Spinocerebellar Ataxias / genetics
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Spinocerebellar Ataxias / metabolism
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Spinocerebellar Ataxias / pathology*
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Trinucleotide Repeat Expansion / genetics
Substances
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ATXN1 protein, human
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Ataxin-1
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Ataxins
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Atxn1 protein, mouse
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Nerve Tissue Proteins
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Nuclear Proteins
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Peptides
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polyglutamine