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Mol Neurobiol (2012) 46:430466 DOI 10.1007/s12035-012-8316-3
The Author(s) 2012. This article is published with open access at Springerlink.com
Mouse Models of Polyglutamine Diseases in Therapeutic Approaches: Review and Data Table. Part II
Pawel M. Switonski & Wojciech J. Szlachcic &
Agnieszka Gabka & Wlodzimierz J. Krzyzosiak &
Maciej Figiel
Received: 22 April 2012 /Accepted: 29 July 2012 /Published online: 4 September 2012 #
Abstract Mouse models of human diseases are created both to understand the pathogenesis of the disorders and to find successful therapies for them. This work is the second part in a series of reviews of mouse models of polyglutamine (polyQ) hereditary disorders and focuses on in vivo experimental therapeutic approaches. Like part I of the polyQ mouse model review, this work is supplemented with a table that contains data from experimental studies of therapeutic approaches in polyQ mouse models. The aim of this review was to characterize the benefits and outcomes of various therapeutic strategies in mouse models. We examine whether the therapeutic strategies are specific to a single disease or are applicable to more than one polyQ disorder in mouse models. In addition, we discuss the suitability of mouse models in therapeutic approaches. Although the majority of therapeutic studies were performed in mouse models of Huntington disease, similar strategies were also used in other disease models.
Keywords Polyglutamine . Mouse models . Therapy .
Huntingtondisease .Spinocerebellarataxia .DRPLA .SBMA
Introduction
Polyglutamine (polyQ) diseases are dominantly inherited disorders caused by mutations in single genes, called
expansions, that result in the excessive elongation of CAG triplet tracts encoding glutamines. This type of mutation usually produces many symptoms that are primarily, but not exclusively, neurological. Currently, nine polyQ diseases have been identified, including Huntington disease (HD); spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7 and 17; dentatorubralpallidoluysian atrophy (DRPLA); and spinal and bulbar muscular atrophy (SBMA). Although the genes where the mutation tracts are located do not belong to common gene families, the pathogenic features caused by the mutations are similar. The symptoms of these disorders include motor impairments such as dystonia and chorea in HD, ataxia in SCAs and general muscle weakness in SBMA, which often confine the patients to a wheelchair. In some cases, serious cognitive deficiencies appear at later stages...