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

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.

• Authors: M Wakamiya, T Matsuura, Y Liu, G C Schuster, R Gao, W Xu, P S Sarkar, X Lin, T Ashizawa
• Journal: Neurology (Neurology) Vol. 67 Issue 4 Pg. 607-13 (Aug 22 2006) ISSN: 1526-632X [Electronic] United States
• PMID: 16924013 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ATXN10 protein, human
• Ataxin-10
• Biomarkers
• Nerve Tissue Proteins

Topics

• Amino Acid Sequence
• Animals
• Ataxin-10
• Biomarkers (metabolism)
• Cells, Cultured
• Fibroblasts (metabolism)
• Humans
• Lymphocytes (metabolism)
• Mice
• Molecular Sequence Data
• Nerve Tissue Proteins (chemistry, metabolism)
• Spinocerebellar Ataxias (metabolism)
• Tissue Distribution