Intranuclear aggregation of nonexpanded ataxin-3 in marinesco bodies of the nonhuman primate substantia nigra.
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.
Kettner
Mattias
M
Department of Anatomy, J. W. Goethe University, Frankfurt/Main, Germany.
Willwohl
Dirk
D
Hubbard
Gene B
GB
Rüb
U
U
Dick
Edward J
EJ
Cox
Ann B
AB
Trottier
Yvon
Y
Auburger
Georg
G
Braak
Heiko
H
Schultz
Christian
C
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
D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025801:Ubiquitin; C092341:ATXN3 protein, human; D000067699:Ataxin-3