The role of ataxin 10 in the pathogenesis of spinocerebellar ataxia type 10.
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.
Wakamiya
M
M
Department of Neurology, University of Texas Medical Branch, Galveston 77555-0539, USA.
Matsuura
T
T
Liu
Y
Y
Schuster
G C
GC
Gao
R
R
Xu
W
W
Sarkar
P S
PS
Lin
X
X
Ashizawa
T
T
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
C503889:ATXN10 protein, human; D000067736:Ataxin-10; D015415:Biomarkers; D009419:Nerve Tissue Proteins