Lentivector‐mediated rescue from cerebellar ataxia in a mouse model of spinocerebellar ataxia
| Autor: | Haruyasu Yamaguchi, Kiyohiko Takayama, Kazuhiro Mitsumura, Chiho Koyama, Hirokazu Hirai, Takashi Torashima, Akira Iizuka, Miho Oue, Shigeru Yanagi |
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| Rok vydání: | 2008 |
| Předmět: |
Cerebellum
Ataxia Transgene Genetic enhancement Genetic Vectors Scientific Report Purkinje cell Mice Transgenic Biology Biochemistry GTP Phosphohydrolases Mice Purkinje Cells Genetics medicine Animals Spinocerebellar Ataxias Molecular Biology Cerebellar ataxia Reverse Transcriptase Polymerase Chain Reaction Lentivirus Dendrites Genetic Therapy medicine.disease Immunohistochemistry Molecular biology Cell biology medicine.anatomical_structure Microscopy Fluorescence Spinocerebellar ataxia Triphosphatase medicine.symptom Peptides |
| Zdroj: | EMBO reports. 9:393-399 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.1038/embor.2008.31 |
| Popis: | Polyglutamine disorders are inherited neurodegenerative diseases caused by the accumulation of expanded polyglutamine protein (polyQ). Previously, we identified a new guanosine triphosphatase, CRAG, which facilitates the degradation of polyQ aggregates through the ubiquitin–proteasome pathway in cultured cells. Because expression of CRAG decreases in the adult brain, a reduced level of CRAG could underlie the onset of polyglutamine diseases. To examine the potential of CRAG expression for treating polyglutamine diseases, we generated model mice expressing polyQ predominantly in Purkinje cells. The model mice showed poor dendritic arborization of Purkinje cells, a markedly atrophied cerebellum and severe ataxia. Lentivector-mediated expression of CRAG in Purkinje cells of model mice extensively cleared polyQ aggregates and re-activated dendritic differentiation, resulting in a striking rescue from ataxia. Our in vivo data substantiate previous cell-culture-based results and extend further the usefulness of targeted delivery of CRAG as a gene therapy for polyglutamine diseases. |
| Databáze: | OpenAIRE |
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