Motor uncoordination and neuropathology in a transgenic mouse model of Machado-Joseph disease lacking intranuclear inclusions and ataxin-3 cleavage products

• Tipo: Artigo em Revista Científica Internacional
• Data: 2010

Autores

Silva Fernandes, A (Autor) Outra; Costa, MD (Autor) Outra; Duarte Silva, S (Autor) Outra; oliveira, p (Autor) ICBAS; Botelho, CM (Autor) Outra; Martins, L (Autor) Outra; Mariz, JA (Autor) Outra; Ferreira, T (Autor) Outra; Ribeiro, F (Autor) Outra; Correia Neves, M (Autor) Outra; Costa, C (Autor) Outra; Maciel, P (Autor) Outra

Revista

Título: Neurobiology of Disease

Vol. 40

Páginas: 163-176

ISSN: 0969-9961

Editora: Elsevier

Indexação

ISI Web of Knowledge - 38 Citações

Scopus - 48 Citações

Outras Informações

ID Authenticus: P-003-2KE

DOI: 10.1016/j.nbd.2010.05.021

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14