Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/29574
Título: | Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products |
Autor(es): | Fernandes, Anabela Silva Costa, Maria do Carmo Silva, Sara Carina Duarte Oliveira, Pedro Botelho, C. M. Martins, Luís Filipe Forte Oliveira Mariz, José Ferreira, Tiago Ribeiro, Filipa Pinto Neves, Margarida Correia Maciel, P. Costa, Cristina |
Palavras-chave: | Polyglutamine Neuronal atrophy Pathogenesis Neuroinflammation Spinocerebellar ataxia Neurodegeneration Genetic instability Triplet repeats |
Data: | Out-2010 |
Editora: | Elsevier 1 |
Revista: | Neurobiology of Disease |
Resumo(s): | Machado-Joseph disease (MJD) is a late-onset neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the ataxin-3 protein. We generated two transgenic mouse lineages expressing the expanded human ataxin-3 under the control of the CMV promoter: CMVMJD83 and CMVMJD94, carrying Q83 and Q94 stretches, respectively. Behavioral analysis revealed that the CMVMJD94 transgenic mice developed motor uncoordination, intergenerational instability of the CAG repeat and a tissue-specific increase in the somatic mosaicism of the repeat with aging. Histopathological analysis of MJD mice at early and late stages of the disease revealed neuronal atrophy and astrogliosis in several brain regions; however, we found no signs of microglial activation or neuroinflammatory response prior to the appearance of an overt phenotype. In our model, the appearance of MJD-like symptoms was also not associated with the presence of ataxin-3 cleavage products or intranuclear aggregates. We propose the transgenic CMVMJD94 mice as a useful model to study the early stages in the pathogenesis of MJD and to explore the molecular mechanisms involved in CAG repeat instability. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/29574 |
DOI: | 10.1016/j.nbd.2010.05.021 |
ISSN: | 0969-9961 |
Versão da editora: | http://www.sciencedirect.com/science/article/pii/S096999611000183X |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
silva-fernandes_ neurobiol dis 2010 posp.pdf | 1,1 MB | Adobe PDF | Ver/Abrir |