title: 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
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurology, University of Texas Medical Branch, Galveston 77555-0539, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wakamiya
authors.forename: T
authors.initials: T
authors.lastname: Matsuura
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: G C
authors.initials: GC
authors.lastname: Schuster
authors.forename: R
authors.initials: R
authors.lastname: Gao
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: P S
authors.initials: PS
authors.lastname: Sarkar
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Ashizawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000067736:Ataxin-10; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D020754:Spinocerebellar Ataxias / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C503889:ATXN10 protein, human; D000067736:Ataxin-10; D015415:Biomarkers; D009419:Nerve Tissue Proteins