title: Intranuclear aggregation of nonexpanded ataxin-3 in marinesco bodies of the nonhuman primate substantia nigra.
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.
authors.affiliation: Department of Anatomy, J. W. Goethe University, Frankfurt/Main, Germany.
authors.forename: Mattias
authors.initials: M
authors.lastname: Kettner
authors.forename: Dirk
authors.initials: D
authors.lastname: Willwohl
authors.forename: Gene B
authors.initials: GB
authors.lastname: Hubbard
authors.forename: U
authors.initials: U
authors.lastname: Rüb
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dick
authors.forename: Ann B
authors.initials: AB
authors.lastname: Cox
authors.forename: Yvon
authors.initials: Y
authors.lastname: Trottier
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
authors.forename: Christian
authors.initials: C
authors.lastname: Schultz
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000067699:Ataxin-3; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D008253:Macaca mulatta; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins; D010215:Papio; D012097:Repressor Proteins; D013378:Substantia Nigra / Q000378:metabolism* / Q000648:ultrastructure; D025801:Ubiquitin / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025801:Ubiquitin; C092341:ATXN3 protein, human; D000067699:Ataxin-3