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Machado‐Joseph disease gene product is a cytoplasmic protein widely expressed in brain
Author(s) -
Paulson Henry L.,
Das Sonal S.,
Crino Peter B.,
Perez Matthew K.,
Patel Sonal C.,
Gotsdiner Denise,
Fischbeck Kenneth H.,
Pittman Randall N.
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410410408
Subject(s) - polyglutamine tract , machado–joseph disease , neurodegeneration , biology , gene product , gene , disease , huntingtin protein , gene expression , microbiology and biotechnology , genetics , mutant , huntingtin , spinocerebellar ataxia , pathology , medicine
Machado‐Joseph disease (MJD) is one of at least six neurodegenerative diseases caused by expansion of a CAG repeat encoding a polyglutamine tract in the disease protein. To study the molecular mechanism of disease, we isolated both normal and expanded repeat MJD1 cDNAs, and generated antiserum against the recombinant gene product, called ataxin‐3. Using this antiserum, we demonstrate that in disease tissue, both the normal and mutant ataxin‐3 protein are expressed throughout the body and in all regions of the brain examined, including areas generally spared by disease. In brain, certain regions (the striatum, for example) express ataxin‐3 in only a limited subset of neurons. Immunolocalization studies in normal and disease brain, and in transfected cells, indicate that ataxin‐3 is predominantly a cytoplasmic protein that localizes to neuronal processes as well. We conclude that in MJD, as in other polyglutamine repeat diseases, cellular expression of the disease gene is not itself sufficient to cause neuronal degeneration; other cell‐specific factors must be invoked to explain the restricted neuropathology seen in MJD. The restricted expression of ataxin‐3 in certain regions, however, may influence the pattern of neurodegeneration and provide clues to the protein's function.