1. Intranuclear Aggregation of Nonexpanded Ataxin-3 in Marinesco Bodies of the Nonhuman Primate Substantia Nigra
- Author
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Kettner, Mattias, Willwohl, Dirk, Hubbard, Gene B., Rüb, U., Dick Jr., Edward J., Cox, Ann B., Trottier, Yvon, Auburger, Georg, Braak, Heiko, and Schultz, Christian
- Subjects
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SUBSTANTIA nigra , *CELLULAR pathology , *CEREBELLAR ataxia - Abstract
Marinesco bodies (MB) are intranuclear inclusion bodies predominantly found in melanin-pigmented neurons of the substantia nigra. MB are demonstrable not only in humans but also in nonhuman primates. In the present study MB of aged rhesus monkeys (Macaca mulatta; n = 15; mean age 16 years) and aged baboons (Papio anubis; n = 13; mean age 25 years) were examined immunohistochemically. MB were found to be immunoreactive for ubiquitin, a protein involved in initiation of proteasome-mediated proteolysis. We also demonstrate that MB in monkeys are intensely immunoreactive for the protein ataxin-3 as detected by using two monoclonal anti-ataxin-3 antibodies (1H9 and 2B6). The abnormally expanded form of this polyglutamine protein is known to be causally involved in spinocerebellar ataxia type 3 or Machado–Joseph disease. The monoclonal antibody 1C2 was employed to examine whether ataxin-3 in MB in monkeys contains such an abnormally expanded polyglutamine stretch. MB were consistently 1C2-immunonegative, indicating that they are composed of normal wild-type ataxin-3. In conclusion MB in nonhuman primates permit experimental examination of mechanisms involved in transnuclear localization, intranuclear aggregation, and ubiquitination of nonexpanded polyglutamine proteins. [Copyright &y& Elsevier]
- Published
- 2002
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