Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/9163 |
Resumo: | Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant ataxia caused by an expansion of CAG repeats in the exon 1 of the gene ATXN2, conferring a gain of toxic function that triggers the appearance of the disease phenotype. SCA2 is characterized by several symptoms including progressive gait ataxia and dysarthria, slow saccadic eye movements, sleep disturbances, cognitive impairments, and psychological dysfunctions such as insomnia and depression, among others. The available treatments rely on palliative care, which mitigate some of the major symptoms but ultimately fail to block the disease progression. This persistent lack of effective therapies led to the development of several models in yeast, C. elegans, D. melanogaster, and mice to serve as platforms for testing new therapeutic strategies and to accelerate the research on the complex disease mechanisms. In this work, we review 4 transgenic and 1 knock-in mouse that exhibit a SCA2-related phenotype and discuss their usefulness in addressing different scientific problems. The knock-in mice are extremely faithful to the human disease, with late onset of symptoms and physiological levels of mutant ataxin-2, while the other transgenic possess robust and well-characterized motor impairments and neuropathological features. Furthermore, a new BAC model of SCA2 shows promise to study the recently explored role of non-coding RNAs as a major pathogenic mechanism in this devastating disorder. Focusing on specific aspects of the behavior and neuropathology, as well as technical aspects, we provide a highly practical description and comparison of all the models with the purpose of creating a useful resource for SCA2 researchers worldwide. |
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Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive reviewSpinocerebellar ataxia type 2 (SCA2) is an autosomal dominant ataxia caused by an expansion of CAG repeats in the exon 1 of the gene ATXN2, conferring a gain of toxic function that triggers the appearance of the disease phenotype. SCA2 is characterized by several symptoms including progressive gait ataxia and dysarthria, slow saccadic eye movements, sleep disturbances, cognitive impairments, and psychological dysfunctions such as insomnia and depression, among others. The available treatments rely on palliative care, which mitigate some of the major symptoms but ultimately fail to block the disease progression. This persistent lack of effective therapies led to the development of several models in yeast, C. elegans, D. melanogaster, and mice to serve as platforms for testing new therapeutic strategies and to accelerate the research on the complex disease mechanisms. In this work, we review 4 transgenic and 1 knock-in mouse that exhibit a SCA2-related phenotype and discuss their usefulness in addressing different scientific problems. The knock-in mice are extremely faithful to the human disease, with late onset of symptoms and physiological levels of mutant ataxin-2, while the other transgenic possess robust and well-characterized motor impairments and neuropathological features. Furthermore, a new BAC model of SCA2 shows promise to study the recently explored role of non-coding RNAs as a major pathogenic mechanism in this devastating disorder. Focusing on specific aspects of the behavior and neuropathology, as well as technical aspects, we provide a highly practical description and comparison of all the models with the purpose of creating a useful resource for SCA2 researchers worldwide.SapientiaAlves-Cruzeiro, João M. da ConceiçãoMendonça, LilianaAlmeida, Luís Pereira deNóbrega, Clévio2017-04-07T15:55:34Z2016-122016-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/9163eng1662-453X10.3389/fnins.2016.00572info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:20:34Zoai:sapientia.ualg.pt:10400.1/9163Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:01:11.050200Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
title |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
spellingShingle |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review Alves-Cruzeiro, João M. da Conceição |
title_short |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
title_full |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
title_fullStr |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
title_full_unstemmed |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
title_sort |
Motor dysfunctions and neuropathology in mouse models of spinocerebellar ataxia type 2: A comprehensive review |
author |
Alves-Cruzeiro, João M. da Conceição |
author_facet |
Alves-Cruzeiro, João M. da Conceição Mendonça, Liliana Almeida, Luís Pereira de Nóbrega, Clévio |
author_role |
author |
author2 |
Mendonça, Liliana Almeida, Luís Pereira de Nóbrega, Clévio |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Alves-Cruzeiro, João M. da Conceição Mendonça, Liliana Almeida, Luís Pereira de Nóbrega, Clévio |
description |
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant ataxia caused by an expansion of CAG repeats in the exon 1 of the gene ATXN2, conferring a gain of toxic function that triggers the appearance of the disease phenotype. SCA2 is characterized by several symptoms including progressive gait ataxia and dysarthria, slow saccadic eye movements, sleep disturbances, cognitive impairments, and psychological dysfunctions such as insomnia and depression, among others. The available treatments rely on palliative care, which mitigate some of the major symptoms but ultimately fail to block the disease progression. This persistent lack of effective therapies led to the development of several models in yeast, C. elegans, D. melanogaster, and mice to serve as platforms for testing new therapeutic strategies and to accelerate the research on the complex disease mechanisms. In this work, we review 4 transgenic and 1 knock-in mouse that exhibit a SCA2-related phenotype and discuss their usefulness in addressing different scientific problems. The knock-in mice are extremely faithful to the human disease, with late onset of symptoms and physiological levels of mutant ataxin-2, while the other transgenic possess robust and well-characterized motor impairments and neuropathological features. Furthermore, a new BAC model of SCA2 shows promise to study the recently explored role of non-coding RNAs as a major pathogenic mechanism in this devastating disorder. Focusing on specific aspects of the behavior and neuropathology, as well as technical aspects, we provide a highly practical description and comparison of all the models with the purpose of creating a useful resource for SCA2 researchers worldwide. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12 2016-12-01T00:00:00Z 2017-04-07T15:55:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/9163 |
url |
http://hdl.handle.net/10400.1/9163 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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1662-453X 10.3389/fnins.2016.00572 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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