title: Spinocerebellar ataxia type 1--modeling the pathogenesis of a polyglutamine neurodegenerative disorder in transgenic mice.
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.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Clark
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D001921:Brain / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002531:Cerebellum / Q000473:pathology / Q000648:ultrastructure; D003391:Cranial Nerves / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009849:Olivopontocerebellar Atrophies / Q000473:pathology; D010455:Peptides / Q000235:genetics*; D011689:Purkinje Cells / Q000473:pathology / Q000648:ultrastructure; D013116:Spinal Cord / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine