Expression of ataxin-2 in brains from normal individuals and patients withAlzheimer's disease and spinocerebellar ataxia 2

Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinuc leotide repeat located in the coding region of the human SCA2 gene. The SCA 2 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 reve aled 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 neur onal groups with strong labeling of Purkinje cells; (3) the level of ataxin -2 increased with age in Purkinje cells of normal individuals; and (4) atax in-2-like immunoreactivity in SCA2 brain tissues was more intense than in n ormal brain tissues, and intranuclear ubiquitinated inclusions were not see n in SCA2 brain tissues.