Distribution of ataxin-7 in normal human brain and retina

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease caused by th e expansion of a CAG repeat encoding a polyglutamine tract in the protein a taxin-7, We developed antibodies directed against two different parts of th e ataxin-7 protein and studied its distribution in brain and peripheral tis sue from healthy subjects. Normal ataxin-7 was widely expressed in brain, r etina and peripheral tissues, including striated muscle, testis and thyroid gland. In the brain, expression of ataxin-7 was not limited to areas in wh ich neurones degenerate, and the level of expression was not related to the severity of neuronal loss. Immunoreactivity was low in some vulnerable pop ulations of neurones, such as Purkinje cells. In neurones, ataxin-7 was fou nd in the cell bodies and in processes. Nuclear labelling was also observed in some neurones, but was not related to the distribution of intranuclear inclusions observed in an SCA7 patient. In this patient, the proportion of neurones with nuclear labelling was higher, on average, in regions with neu ronal loss. Double immunolabelling coupled with confocal microscopy showed that ataxin-7 colocalized with BiP, a marker of the endoplasmic reticulum, but not with markers of mitochondria or the trans-Golgi network.