Expression analysis of ataxin-7 mRNA and protein in human brain: evidence for a widespread distribution and focal protein accumulation.
Spinocerebellar ataxia 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG-trinucleotide repeat in the coding region of the SCA7 gene. The expansion is translated into an extended polyglutamine stretch in the protein ataxin-7, a protein of unknown function. By Northern blot analysis expression of ataxin-7 was detected in numerous regions of human brain and some peripheral tissues. It is unknown, however, if ataxin-7 is enriched at sites of the SCA7 pathology. We studied the regional and cellular expression pattern of ataxin-7 at the mRNA level by in situ hybridization histochemistry in normal human brain. Furthermore we used a monoclonal and two polyclonal antibodies raised against the normal ataxin-7 to establish the distribution of this protein in brain, retina and peripheral organs. At the mRNA level ataxin-7 was preferentially expressed in neurons; the regional distribution reflected neuronal packing density. Ataxin-7 immunoreactivity (IR) was similarly widely expressed. In most neurons, ataxin-7 IR was preferentially localized to the cytoplasmatic compartment although some nuclear ataxin-7 IR was detected in most neurons. A more intense and more prominently nuclear ataxin-7 IR was observed in neurons of the pons and the inferior olive, brain regions severly affected by the disease, suggesting that the subcellular localization and abundance of ataxin-7 is regulated in a regionally specific way. Since neurons displaying more intense and more prominently nuclear ataxin-7 IR belonged to the class of susceptible cells in SCA7, an enrichment of normal ataxin-7 in the nuclear compartment may contribute to neurodegeneration. However not all sites of SCA7 pathology displayed a strong cytoplasmatic and nuclear immunoreactivity.
Lindenberg
K S
KS
Department of Neurology, Albert Ludwigs-University, Freiburg, Germany.
Yvert
G
G
Müller
K
K
Landwehrmeyer
G B
GB
D000067719:Ataxin-7; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D006651:Histocytochemistry; D006801:Humans; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger