| Autor: |
Veronica F. Colomer Gould, Daniel Goti, Donna Pearce, Guillermo A. Gonzalez, Hong Gao, Mario Bermudez de Leon, Nancy A. Jenkins, Neal G. Copeland, Christopher A. Ross, Dale R. Brown |
| Jazyk: |
angličtina |
| Rok vydání: |
2007 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 27, Iss 3, Pp 362-369 (2007) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2007.06.005 |
| Popis: |
Machado–Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3). Neuronal loss in MJD/SCA3 is associated with a mutant ataxin-3 toxic fragment. Defining mutant ataxin-3 proteolytic site(s) could facilitate the identification of the corresponding enzyme(s). Previously, we reported a mutant ataxin-3 mjd1a fragment in the brain of transgenic mice (Q71) that contained epitopes C-terminal to amino acid 220. In this study, we generated and characterized neuroblastoma cells and transgenic mice expressing mutant ataxin-3 mjd1a lacking amino acids 190–220 (deltaQ71). Less deltaQ71 than Q71 fragments were detected in the cell but not mouse model. The transgenic mice developed an MJD/SCA3-like phenotype and their brain homogenates had a fragment containing epitopes C-terminal to amino acid 220. Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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