title: Gene expression in Huntington's disease skeletal muscle: a potential biomarker.
abstract: 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, Hdh(CAG(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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research center, Seattle, WA 98109, USA. astrand@fhcrc.org
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Strand
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: Dennis
authors.initials: D
authors.lastname: Shaw
authors.forename: Thomas
authors.initials: T
authors.lastname: Bird
authors.forename: Janice
authors.initials: J
authors.lastname: Holton
authors.forename: Christopher
authors.initials: C
authors.lastname: Turner
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tapscott
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Schapira
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
mesh_terms: D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015415:Biomarkers