The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10

M. Wakamiya, T. Matsuura, Y. Liu, G. C. Schuster, R. Gao, W. Xu, Partha Sarkar, X. Lin, T. Ashizawa

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. SCA10 is caused by an expansion of an ATTCT pentanucleotide repeat in intron 9 of the ataxin 10 (ATXN10) gene encoding an approximately 55-kd protein of unknown function. However, how this mutation leads to SCA10 is unknown. METHODS: In an effort to understand the pathogenic mechanism of SCA10, the authors conducted a series of experiments to address the effect of repeat expansion on the transcription and RNA processing of the ATXN10 gene. In addition, we generated Sca10 (mouse ataxin 10 homolog)-null mice and addressed the role of Sca10 gene dosage on the cerebellum. RESULTS: Mutant ATXN10 allele is transcribed at the normal level, and the pre-mRNA containing an expanded repeat is processed normally in patient-derived cells. Sca10-null mice exhibited embryonic lethality. Heterozygous mutants were overtly normal and did not develop SCA10 phenotype CONCLUSION: A simple gain of function or loss of function of ATXN10 is unlikely to be the major pathogenic mechanism contributing to the spinocerebellar ataxia type 10 phenotype.

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalNeurology
Volume67
Issue number4
DOIs
StatePublished - Aug 2006

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Phenotype
Spinocerebellar Ataxia 10
Ataxin-10
Cerebellar Ataxia
Gene Dosage
RNA Precursors
Microsatellite Repeats
Introns
Cerebellum
Genes
Seizures
Alleles
RNA
Mutation
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Wakamiya, M., Matsuura, T., Liu, Y., Schuster, G. C., Gao, R., Xu, W., ... Ashizawa, T. (2006). The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10. Neurology, 67(4), 607-613. https://doi.org/10.1212/01.wnl.0000231140.26253.eb

The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10. / Wakamiya, M.; Matsuura, T.; Liu, Y.; Schuster, G. C.; Gao, R.; Xu, W.; Sarkar, Partha; Lin, X.; Ashizawa, T.

In: Neurology, Vol. 67, No. 4, 08.2006, p. 607-613.

Research output: Contribution to journalArticle

Wakamiya, M, Matsuura, T, Liu, Y, Schuster, GC, Gao, R, Xu, W, Sarkar, P, Lin, X & Ashizawa, T 2006, 'The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10', Neurology, vol. 67, no. 4, pp. 607-613. https://doi.org/10.1212/01.wnl.0000231140.26253.eb
Wakamiya M, Matsuura T, Liu Y, Schuster GC, Gao R, Xu W et al. The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10. Neurology. 2006 Aug;67(4):607-613. https://doi.org/10.1212/01.wnl.0000231140.26253.eb
Wakamiya, M. ; Matsuura, T. ; Liu, Y. ; Schuster, G. C. ; Gao, R. ; Xu, W. ; Sarkar, Partha ; Lin, X. ; Ashizawa, T. / The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10. In: Neurology. 2006 ; Vol. 67, No. 4. pp. 607-613.
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