title: Regional and cellular expression of the Machado-Joseph disease gene in brains of normal and affected individuals.
abstract: Machado-Joseph disease (MJD) is an autosomal dominant disorder characterized pathologically by spinocerebellar degeneration. Recently, an expansion of CAG repeat in a gene located at the chromosome 14q32.1 was found to be responsible for the disease. Here, we investigated in situ the expression of the MJD gene (MJD1) in the central nervous systems of normal and affected individuals and in rat brains. This gene was expressed in all regions of rat and human normal brains with certain regional variations. MJD1 was transcribed preferentially in neurons, although low levels of MJD1 mRNA were also observed in glial cells. Neurons susceptible to degeneration in MJD expressed MJD1 but not selectively. In the affected brains, the MJD1 mRNA distribution and amount in all the areas examined were similar in patients and controls. In addition, the cellular MJD1 mRNA level correlated neither with clinical severity nor expanded length. Our study showed that the expression levels of trinucleotide repeats in MJD patients and normal controls did not differ, indicating that the pathogenesis of MJD may involve direct toxicity to vulnerable subsets and/or region-specific cofactors of MJD proteins.
authors.affiliation: Department of Neurology, Institute for Brain Research, School of Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishiyama
authors.forename: S
authors.initials: S
authors.lastname: Murayama
authors.forename: J
authors.initials: J
authors.lastname: Goto
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Hashida
authors.forename: S
authors.initials: S
authors.lastname: Katayama
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000818:Animals; D000067699:Ataxin-3; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012016:Reference Values; D012097:Repressor Proteins; D014158:Transcription, Genetic; D018911:Trinucleotide Repeats
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3; C511593:Atxn3 protein, rat