Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2.
Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinucleotide repeat located in the coding region of the human SCA2 gene. The SCA2 gene product, ataxin-2, is a basic protein with two domains (Sm1 and Sm2) implicated in RNA splicing and protein interaction. However, the wild-type function of ataxin-2 is yet to be determined. To help clarify the function of ataxin-2, we produced antibodies to three antigenic peptides of ataxin-2 and analyzed the expression pattern of ataxin-2 in normal and SCA2 adult brains and cerebellum at different developmental stages. These studies revealed that (1) both wild-type and mutant forms of ataxin-2 were synthesized; (2) the wild-type ataxin-2 was localized in the cytoplasm in specific neuronal groups with strong labeling of Purkinje cells; (3) the level of ataxin-2 increased with age in Purkinje cells of normal individuals; and (4) ataxin-2-like immunoreactivity in SCA2 brain tissues was more intense than in normal brain tissues, and intranuclear ubiquitinated inclusions were not seen in SCA2 brain tissues.
Huynh
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DP
CSMC Burns and Allen Research Institute, and Division of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Del Bigio
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MR
Ho
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DH
Pulst
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SM
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000067528:Ataxins; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000032:analysis*; D013132:Spinocerebellar Degenerations / Q000378:metabolism*