Journal Article

Gene expression in Huntington's disease skeletal muscle: a potential biomarker

Andrew D. Strand, Aaron K. Aragaki, Dennis Shaw, Thomas Bird, Janice Holton, Christopher Turner, Stephen J. Tapscott, Sarah J. Tabrizi, Anthony H. Schapira, Charles Kooperberg and James M. Olson

in Human Molecular Genetics

Volume 14, issue 13, pages 1863-1876
Published in print July 2005 | ISSN: 0964-6906
Published online May 2005 | e-ISSN: 1460-2083 | DOI:
Gene expression in Huntington's disease skeletal muscle: a potential biomarker

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Huntington's disease (HD) is an incurable and fatal neurodegenerative disorder. Improvements in the objective measurement of HD will lead to more efficient clinical trials and earlier therapeutic intervention. We hypothesized that abnormalities seen in the R6/2 mouse, a greatly accelerated HD model, might highlight subtle phenotypes in other mouse models and human HD. In this paper, we identify common gene expression changes in skeletal muscle from R6/2 mice, HdhCAG(150) homozygous knock-in mice and HD patients. This HD-triggered gene expression phenotype is consistent with the beginnings of a transition from fast-twitch to slow-twitch muscle fiber types. Metabolic adaptations similar to those induced by diabetes or fasting are also present but neither metabolic disorder can explain the full phenotype of HD muscle. The HD-induced gene expression changes reflect disease progression. This raises the possibility that muscle gene expression may be used as an objective biomarker to complement clinical HD-rating systems. Furthermore, an understanding of the molecular basis of muscle dysfunction in HD should provide insight into mechanisms involved in neuronal abnormalities and neurodegeneration.

Journal Article.  10441 words.  Illustrated.

Subjects: Genetics and Genomics

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