Distribution of ataxin-7 in normal human brain and retina

Abstract

Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disease caused by the expansion of a CAG repeat encoding a polyglutamine tract in the protein ataxin-7. We developed antibodies directed against two different parts of the ataxin-7 protein and studied its distribution in brain and peripheral tissue from healthy subjects. Normal ataxin-7 was widely expressed in brain, retina and peripheral tissues, including striated muscle, testis and thyroid gland. In the brain, expression of ataxin-7 was not limited to areas in which neurones degenerate, and the level of expression was not related to the severity of neuronal loss. Immunoreactivity was low in some vulnerable populations of neurones, such as Purkinje cells. In neurones, ataxin-7 was found 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 neuronal 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.

A Conditional Pan-NeuronalDrosophilaModel of Spinocerebellar Ataxia 7 with a Reversible Adult Phenotype Suitable for Identifying Modifier Genes

“…Because ATXN7 is widely expressed in humans (David et al, 1997;Cancel et al, 2000), but alterations are only observed in neurons, expression of the transgenes was targeted both ubiquitously using the da-GAL4 strain and in all neurons of the peripheral nervous system and CNS using the elav C155 -GAL4 line. To determine whether the truncated forms of human ATXN7 are expressed and processed normally in Drosophila, ATXN7T expression in the SCA7T-10Q and SCA7T-102Q da-GAL4 lines were analyzed on Western blots of larval extracts.…”

Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy

“…56,66 Indeed, a short N-terminal fragment of mutant ataxin-7 aggregates more readily than the full-length protein in transfected cells. 62 In addition, ataxin-7 inclusions arise exclusively in the nucleus, even in neurons with primarily Figure 7 SCA7 NI.…”

“…56 Hence, truncation of ataxin-7 might further promote its localization within the nucleus, where it perhaps exhibits faster aggregation and greater toxicity. Importantly, restricted occurrence of such proteolytic events might partly determine the selective patterns of neurodegeneration in SCA7.…”

Spinocerebellar ataxia 7 (SCA7)

“…Neuropathological examination reveals moderate to severe neuronal loss and gliosis in the cerebellum and associated structures (inferior olive, cerebellar cortex, dentate nucleus, pontine nuclei), the basal ganglia (globus pallidus, substantia nigra, subthalamic nucleus, red nucleus) and the spinal cord (Enevoldson et al, 1994;Gouw et al, 1994;Martin et al, 1994;Cancel et al, 2000). Spinocerebellar, olivocerebellar and efferent cerebellar tracts are severely affected.…”